Skip to main content
SpringerLink
Log in
Book cover

Reviews of Physiology, Biochemistry and Pharmacology, Volume 139 pp 33–87Cite as

Voltage-dependent calcium channels: From structure to function

  • Chapter
  • First Online:

Part of the book series: Reviews of Physiology, Biochemistry and Pharmacology ((REVIEWS,volume 139))

Abstract

Voltage-activated calcium channels regulate the intracellular calcium concentration and contribute thereby to calcium signalling in numerous cell types. These channels are widely distributed in the animal kingdom and are an essential part of many excitable and non-excitable mammalian cells. The opening of these channels is primarily regulated by the membrane potential, but is also modulated by a wide variety of hormones, protein kinases, protein phosphatases, toxins and drugs. Site-directed mutagenesis has identified sites on these channels, which interact specifically with other proteins, inhibitors and ions. This article will focus on these recent developments. The older findings have been summarized in several excellent reviews (Striessnig et al. 1993; Hofmann et al. 1994; Catterall 1995; De Waard et al. 1996a).

This is a preview of subscription content, log in via an institution.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Abbreviations

HVA:

high-voltage-activated

LVA:

low-voltage-activated

DHP:

dihydropyridine

PAA:

phenylalkylamine

BTZ:

benzothiazepine

HEK:

human embryonic kidney

HP:

holding potential

RyR:

ryanodine receptor

SNAP:

synaptosome-associated protein

ER:

endoplasmic reticulum

VAMP:

vesicle-associated membrane protein

SNARE:

synaptic core complex

AID:

alpha subunit interaction domain

BID:

beta subunit interaction domain

IC50 :

half-maximal inhibition concentration

AKAP:

A-kinase anchoring protein

PKC:

protein kinase C

FHM:

familial hemiplegic migraine

EA:

episodic ataxia

References

  • Adams B, Tanabe T (1997) Structural regions of the cardiac Ca channel α subunit involved in Ca-dependent inactivation. J Gen Physiol 110:379–389

    Google Scholar 

  • Angelotti T, Hofmann F (1996) Tissue-specific expression of splice variants of the mouse voltage-gated calcium channel α2δ subunit. FEBS Lett 392:331–337

    Google Scholar 

  • Armstrong CM, Neyton J (1991) Ion permeation through calcium channels. A one-site model. Ann N Y Acad Sci 635:18–25

    Google Scholar 

  • Artalejo CR, Rossie S, Perlman RL, Fox AP (1992) Voltage-dependent phosphorylation may recruit Ca2+ current facilitation in chromaffin cells. Nature 358:63–66

    Google Scholar 

  • Babitch J (1990) Channel hands. Nature 346:321–322

    Google Scholar 

  • Bangalore R, Baindur N, Rutledge A, Triggle DJ, Kass RS (1994) L-type calcium channels: asymmetrical intramembrane binding domain revealed by variable length, permanently charged 1,4-dihydropyridines. Mol Pharmacol 46:660–666

    Google Scholar 

  • Bangalore R, Mehrke G, Gingrich K, Hofmann F, Kass RS (1996) Influence of the L-type Ca-channel α2/δ subunit on ionic and gating current in transiently transfected HEK 293 cells. Am J Physiol 270:H1521–H1528

    Google Scholar 

  • Beam KG, Adams BA, Niidome T, Numa S, Tanabe T (1992) Function of a truncated dihydropyridine receptor as both voltage sensor and calcium channel. Nature 360:169–171

    Google Scholar 

  • Bean BP (1989) Neurotransmitter inhibition of neuronal calcium currents by changes in channel voltage dependence. Nature 340:153–156

    Google Scholar 

  • Bech-Hansen NT, Naylor MJ, Maybaum TA, Pearce WG, Koop B, Fishman GA, Mets M, Musarella MA, Boycott KM (1998) Loss-of-function mutations in a calcium-channel α1 subunit in Xp11.23 cause incomplete X-linked congenital stationary night blindness. Nature Genet 19:264–267

    Google Scholar 

  • Beurg M, Sukhareva M, Strube C, Powers PA, Gregg RG, Coronado R (1997) Recovery of Ca2+ current, charge movements, and Ca2+ transients in myotubes deficient in dihydropyridine receptor β1 subunit transfected with beta 1 cDNA. Biophys J 73:807–818

    Google Scholar 

  • Bichet D, Cornet V, Carlier E, Geib S, Volson S, Hoshi T, De Waard M (1999) The I–II loop of Ca2+ channel α1 subunit contains a ß-dependent ER retention signal. Biophys J 76:A91

    Google Scholar 

  • Biel M, Hullin R, Freundner S, Singer D, Dascal N, Flockerzi V, Hofmann F (1991) Tissue-specific expression of high-voltage-activated dihydropyridine-sensitive L-type calcium channels. Eur J Biochem 200:81–88

    Google Scholar 

  • Biel M, Ruth P, Bosse E, Hullin R, Stühmer W, Flockerzi V, Hofmann F (1990) Primary structure and functional expression of a high voltage activated calcium channel from rabbit lung. FEBS Lett 269:409–412

    Google Scholar 

  • Bodi I, Yamaguchi H, Hara M, He M, Schwartz A, Varadi G (1997) Molecular studies on the voltage dependence of dihydropyridine action on L-type Ca2+ channels. Critical involvement of tyrosine residues in motif IIIS6 and IVS6. J Biol Chem 272:24952–24960

    Google Scholar 

  • Bosse E, Regulla S, Biel M, Ruth P, Meyer HE, Flockerzi V, Hofmann F (1990) The cDNA and deduced amino acid sequence of the γ subunit of the L-type calcium channel from rabbit skeletal muscle. FEBS Lett 267:153–156

    Google Scholar 

  • Bourinet E, Charnet P, Tomlinson WJ, Stea A, Snutch TP, Nargeot J (1994) Voltage-dependent facilitation of a neuronal α1c L-type calcium channel. EMBO J 13:5032–5039

    Google Scholar 

  • Bouron A, Soldatov NM, Reuter H (1995) The β1-subunit is essential for modulation by protein kinase C of an human and a non-human L-type Ca2+ channel. FEBS Lett 377:159–162

    Google Scholar 

  • Brown JP, Gee NS (1998) Cloning and deletion mutagenesis of the α2δ calcium channel subunit from porcine cerebral cortex. Expression of a soluble form of the protein that retains [3H]gabapentin binding activity. J Biol Chem 273:24458–24465

    Google Scholar 

  • Burgess DL, Jones JM, Meisler MH and Noebels JL (1997) Mutation of the Ca2+ channel β subunit gene Cchb4 is associated with ataxia and seizures in the lethargic (lh) mouse. Cell 88:385–392

    Google Scholar 

  • Burgess DL, Jones JM, Meisler MH, Noebels JL (1997) Mutation of the Ca2+ channel β subunit gene Cchb4 is associated with ataxia and seizures in the lethargic (lh) mouse. Cell 88:385–392

    Google Scholar 

  • Cai D, Mulle JG, Yue DT (1997) Inhibition of recombinant Ca2+ channels by benzothiazepines and phenylalkylamines: class-specific pharmacology and underlying molecular determinants. Mol Pharmacol 51:872–881

    Google Scholar 

  • Campbell V, Berrow NS, Fitzgerald EM, Brickley K, Dolphin AC (1995) Inhibition of the interaction of G protein Go with calcium channels by the calcium channel β-subunit in rat neurones. J Physiol 485:365–372

    Google Scholar 

  • Castellano A, Wei X, Birnbaumer L, Perez-Reyes E (1993) Cloning and expression of a neuronal calcium channel β subunit. J Biol Chem 268:12359–12366

    Google Scholar 

  • Catterall WA (1995) Structure and function of voltage-gated ion channels. Annu Rev Biochem 64:493–531

    Google Scholar 

  • Catterall WA, Striessnig J (1992) Receptor sites for Ca2+ channel antagonists. Trends Pharmacol Sci 13:256–262

    Google Scholar 

  • Cavalié A, Murakami M, Fleischmann B, Ludwig A, Schroth G, Trost C, Hescheler J, Schwegler H, Flockerzi V (1998) Ca channel function in β3 deficient mice. N-Sch Archiv Pharmacol 358:R163

    Google Scholar 

  • Cens T, Restituito S, Vallentin A, Charnet P (1998) Promotion and inhibition of L-type Ca2+ channel facilitation by distinct domains of the subunit. J Biol Chem 273:18308–18315

    Google Scholar 

  • Charvin N, Leveque C, Walker D, Berton F, Raymond C, Kataoka M, Shoji-Kasai Y, Takahashi M, De Waard M, Seagar MJ (1997) Direct interaction of the calcium sensor protein synaptotagmin I with a cytoplasmic domain of the α1A subunit of the P/Q-type calcium channel. EMBO J 16:4591–4596

    Google Scholar 

  • Chaudhari N (1992) A single nucleotide deletion in the skeletal muscle-specific calcium channel transcript of muscular dysgenesis (mdg) mice. J Biol Chem 267:25636–25639

    Google Scholar 

  • Chavis P, Fagni L, Lansman JB, Bockaert J (1996) Functional coupling between ryanodine receptors and L-type calcium channels in neurons. Nature 382:719–722

    Google Scholar 

  • Chen XH, Tsien RW (1997) Aspartate substitutions establish the concerted action of P-region glutamates in repeats I and III in forming the protonation site of L-type Ca2+ channels. J Biol Chem 272:30002–30008

    Google Scholar 

  • Chien AJ, Carr KM, Shirokov RE, Rios E, Hosey MM (1996) Identification of palmitoylation sites within the L-type calcium channel β2a subunit and effects on channel function. J Biol Chem 271:26465–26468

    Google Scholar 

  • Chien J, Gao TY, Perez-Reyes E, Hosey MM (1998) Membrane targeting of L-type calcium channels-Role of palmitoylation in the subcellular localization of the β2a subunit. J Biol Chem 273:23590–23597

    Google Scholar 

  • Chuang RSI, Jaffe H, Cribbs L, Perez-Reyes E, Swartz KJ (1998) Inhibition of T-type voltage-gated calcium channel by a new scorpion toxin. Nature Neurosci 1:668–674

    Google Scholar 

  • Cribbs LL, Lee JH, Yang J, Satin J, Zhang Y, Daud A, Barclay J, Williamson MP, Fox M, Rees M, PerezReyes E (1998) Cloning and characterization of α 1H from human heart, a member of the T-type Ca2+ channel gene family. Circ Res 83:103–109

    Google Scholar 

  • Dai S, Klugbauer N, Zong X, Seisenberger S, Hofmann F (1999) The role of subunit composition on prepulse facilitation of the cardiac L-type calcium channel. FEBS Lett 442:70–74

    Google Scholar 

  • De Jongh KS, Murphy BJ, Colvin AA, Hell JW, Takahashi M, Catterall WA (1996) Specific phosphorylation of a site in the full-length form of the α1 subunit of the cardiac L-type calcium channel by adenosine 3′,5′-cyclic monophosphate-dependent protein kinase. Biochemistry 35:10392–10402

    Google Scholar 

  • De Jongh KS, Warner C, Colvin AA, Catterall WA (1991) Characterization of two size forms of the α1 subunit of skeletal muscle L-type calcium channels. Proc Natl Acad Sci USA 88:10778–10782

    Google Scholar 

  • de Leon M, Wang Y, Jones L, Perez-Reyes E, Wie X, Soong TW, Snutch TP, Yue DT (1995) Essential Ca2+-binding motif for Ca2+-sensitive inactivation of L-type Ca2+ channels. Science 270:1502–1506

    Google Scholar 

  • De Waard M, Campbell KP (1995a) Subunit regulation of the neuronal α1A Ca2+ channel expressed in Xenopus oocytes. J Physiol 485:619–634

    Google Scholar 

  • De Waard M, Gurnett CA, Campbell KP (1996a) Structural and functional diversity of voltage-activated calcium channels. Ion Channels 4:41–87

    Google Scholar 

  • De Waard M, Pragnell M, Campbell, KP (1994) Ca2+ channel regulation by a conserved β subunit domain. Neuron 13:495–503

    Google Scholar 

  • De Waard M, Scott VE, Pragnell M, Campbell KP (1996b) Identification of critical amino acids involved in α1-β interaction in voltage-dependent Ca2+ channels. FEBS Lett 380:272–276

    Google Scholar 

  • De Waard M, Witcher DR, Pragnell M, Liu H, Campbell KP (1995b) Properties of the α1–β anchoring site in voltage-dependent Ca2+ channels. J Biol Chem 270:12056–12064

    Google Scholar 

  • De Waard M, Liu H, Walker D, Scott VE, Gurnett CA, Campbell KP (1997) Direct binding of G-protein βγ complex to voltage-dependent calcium channels. Nature. 385:446–450

    Google Scholar 

  • Dirksen RT, Nakai J, Gonzalez A, Imoto K, Beam KG (1997) The S5–S6 linker of repeat I is a critical determinant of L-type Ca2+ channel conductance. Biophys J 73:1402–1409

    Google Scholar 

  • Doyle DA, Cabral JM, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT, MacKinnon R (1998) The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280:69–77

    Google Scholar 

  • Dubel SJ, Starr TVB, Hell J, Ahlijanian MK, Enyart JJ, Catterall WA, Snutch TP (1992) Molecular cloning of the α1 subunit of an θ-conotoxin-sensitive calcium channel. Proc Natl Acad Sci USA 89:5058–5062

    Google Scholar 

  • Eberst R, Dai S, Klugbauer N, Hofmann F (1997) Identification and functional characterization of a calcium channel γ subunit Pflügers Arch 433:633–637

    Google Scholar 

  • El-Hayek R, Antoniu B, Wang J, Hamilton SL, Ikemoto N (1995) Identification of calcium release-triggering and blocking regions of the II–III loop of the skeletal muscle dihydropyridine receptor. J Biol Chem 270:22116–22118

    Google Scholar 

  • El-Hayek R, Ikemoto N (1998) Identification of the minimum essential region in the II–III loop of the dihydropyridine receptor α 1 subunit required for activation of skeletal muscle-type excitation-contraction coupling. Biochemistry 37:7015–7020

    Google Scholar 

  • Ellinor PT, Yang J, Sather WA, Zhang JF, Tsien, RW (1995) Ca2+ channel selectivity at a single locus for high-affinity Ca2+ interactions. Neuron 15:1121–1132

    Google Scholar 

  • Ellinor PT, Zhang J-F, Horne WA, Tsien RW (1994) Structural determinants of the blockade of N-type calcium channels by a peptide neurotoxin. Nature 372:272–275

    Google Scholar 

  • Ellinor PT, Zhang JF, Randall AD, Zhou M, Schwarz TL, Tsien RW, Horne WA (1993) Functional expression of a rapidly inactivating neuronal calcium channel. Nature 363:455–458

    Google Scholar 

  • Ellis SB, Williams ME, Ways NR, Ellis SB, Brenner R, Sharp AH, Leung AT, Campbell KP, McKenna E, Koch WJ, Hui A, et al. (1988) Sequence and expression of mRNAs encoding the α1 and α2 subunits of a DHP-sensitive calcium channel. Science 241:1661–1664

    Google Scholar 

  • Felix R, Gurnett CA, De Waard M, Campbell KP (1997) Dissection of functional domains of the voltage-dependent Ca2+ channel α2δ subunit. J Neurosci 17:6884–6891

    Google Scholar 

  • Fletcher CF, Lutz CM, O'Sullivan TN, Shaughnessy JD Jr, Hawkes R, Frankel WN, Copeland NG, Jenkins NA (1996) Absence epilepsy in tottering mutant mice is associated with calcium channel defects. Cell 87:607–617

    Google Scholar 

  • Fouad G, Dalakas M, Servidei S, Mendell JR, Van den Bergh P, Angelini C, Alderson K, Griggs RC, Tawil R, Gregg R, Hogan K, Powers PA, Weinberg N, Malonee W, Ptacek LJ (1997) Genotype-phenotype correlations of DHP receptor α1-subunit gene mutations causing hypokalemic periodic paralysis. Neuromuscul Disord 7:33–38

    Google Scholar 

  • Freise D, Wissenbach U, Bosse-Donecke E, Pfeifer A, Biel M, Hofmann F, Flockerzi V (1998) A gene targeting approach to analyze the role of the L-type calcium channel γ-subunit in the murine skeletal muscle. N-Sch Archiv Pharmacol 358:R71

    Google Scholar 

  • Fujita Y, Mynlieff M, Dirksen RT, Kim MS, Niidome T, Nakai J, Friedrich T, Iwabe N, Miyata T, Furuichi T, Furutama D, Mikoshiba K, Mori Y, Beam KG (1993) Primary structure and functional expression of the ω-conotoxin-sensitive N-type channel from rabbit brain. Neuron 10:585–598

    Google Scholar 

  • Furukawa T, Nukada T, Mori Y, Wakamori M, Fujita Y, Ishida H, Fukuda K, Kato S, Yoshii M (1998a) Differential interactions of the C terminus and the cytoplasmic I–II loop of neuronal Ca2+ channels with G-protein α and βγ subunits — I. Molecular determination. J Biol Chem 273:17585–17594

    Google Scholar 

  • Furukawa T, Miura R, Mori Y, Strobeck M, Suzuki K, Ogihara Y, Asano T, Morishita R, Hashii M, Higashida H, Yoshii M, Nukada T (1998b) Differential interactions of the C terminus and the cytoplasmic I–II loop of neuronal Ca2+ channels with G-protein α and βγ subunits — II. Evidence for direct binding. J Biol Chem 273:17595–17603

    Google Scholar 

  • Gao T, Chien AJ, Hosey MM (1999) Complexes of the αIC and β subunits generate the necessary signal for membrane targeting of class C L-type calcium channels. J Biol Chem 274:2137–2144

    Google Scholar 

  • Gao T, Yatani A, Dell'Acqua ML, Sako H, Green SA, Dascal N, Scott JD, Hosey MM (1997) cAMP-dependent regulation of cardiac L-type Ca2+ channels requires membrane targeting of PKA and phosphorylation of channel subunits. Neuron 19:185–196

    Google Scholar 

  • Garcia AG, Carbone E (1996) Calcium-current facilitation in chromaffin cells. Trends Neurosci 19:383–384

    Google Scholar 

  • Garcia J, Nakai J, Imoto K, Beam KG (1997) Role of S4 segments and the leucine heptad motif in the activation of an L-type calcium channel. Biophys J 72:2515–2523

    Google Scholar 

  • Gee NS, Brown JP, Dissanayake VU, Offord J, Thurlow R, Woodruff GN (1996) The novel anticonvulsant drug, gabapentin (Neurontin), binds to the α2δ subunit of a calcium channel. J Biol Chem 271:5768–5776

    Google Scholar 

  • Gollasch M, Ried C, Liebold M, Haller H, Hofmann F, Luft FC (1996) High permeation of L-type calcium channels at physiological calcium concentrations: homogeity and dependence on the α1 subunit. Am J Physiol 271:C842–C850

    Google Scholar 

  • Grabner M, Wang Z, Hering S, Striessnig J, Glossmann H (1996) Transfer of 1,4-dihydropyridine sensitivity from L-type to class A (BI) calcium channels. Neuron 16:207–218

    Google Scholar 

  • Gray PC, Johnson BD, Westenbroek RE, Hays LG, Yates JR3rd, Scheuer T, Catterall WA, Murphy BJ (1998) Primary structure and function of an A kinase anchoring protein associated with calcium channels. Neuron 20:1017–1026

    Google Scholar 

  • Gregg RG, Messing A, Strube C, Beurg M, Moss R, Behan M, Sukhareva M, Haynes S, Powell JA, Coronado R, Powers PA (1996) Absence of the β subunit (cchb1) of the skeletal muscle dihydropyridine receptor alters expression of the α1 subunit and eliminates excitation-contraction coupling. Proc Natl Acad Sci USA 93:13961–13966

    Google Scholar 

  • Gurnett CA, De Waard M, Campbell KP (1996) Dual function of the voltage-dependent Ca2+ channel a2/δ subunit in current stimulation and subunit interaction. Neuron 16:431–440

    Google Scholar 

  • Gurnett CA, Felix R, Campbell KP (1997) Extracellular interaction of the voltage-dependent Ca2+ channel α2δ and α1 subunits. J Biol Chem 272:18508–18512

    Google Scholar 

  • Guy HR, Conti F (1990) Pursuing the structure and function of voltage-gated channels. Trends Neurosci 13:201–206

    Google Scholar 

  • Haase H, Karczewski P, Beckert R, Krause EG (1993) Phosphorylation of the L-type calcium channel β subunit is involved in β-adrenergic signal transduction in canine myocardium. FEBS Lett 335:217–222

    Google Scholar 

  • Hartzell HC, Fischmeister R (1992) Direct regulation of cardiac Ca2+ channels by G proteins: neither proven nor necessary? Trends Pharmacol Sci 13:380–385

    Google Scholar 

  • He M, Bodi I, Mikala G, Schwartz A (1997) Motif III S5 of L-type calcium channels is involved in the dihydropyridine binding site. A combined radioligand binding and electrophysiological study. J Biol Chem 272:2629–2633

    Google Scholar 

  • Hering S, Aczel S, Grabner M, Doring F, Berjukow S, Mitterdorfer J, Sinnegger MJ, Striessnig J, Degtiar VE, Wang Z, Glossmann H (1996) Transfer of high sensitivity for benzothiazepines from L-type to class A (BI) calcium channels. J Biol Chem 271:24471–24475

    Google Scholar 

  • Herlitze S, Garcia DE, Mackie K, Hille B, Scheuer T, Catterall WA (1996) Modulation of Ca2+ channels by G-protein βγ subunits. Nature 380:258–262

    Google Scholar 

  • Herlitze S, Hockerman GH, Scheuer T, Catterall WA (1997) Molecular determinants of inactivation and G protein modulation in the intracellular loop connecting domains I and II of the calcium channel α1A subunit. Proc Natl Acad Sci USA 94:1512–1516

    Google Scholar 

  • Hescheler J, Pelzer D, Trube G, Trautwein W (1982) Does the organic calcium channel blocker D600 act from inside or outside on the cardiac cell membrane? Pflügers Arch 393:287–291

    Google Scholar 

  • Hescheler J, Schultz G (1993) G-proteins involved in the calcium channel signalling system. Curr Opin Neurobiol 3:360–367

    Google Scholar 

  • Hescheler J, Trautwein W (1988) Modification of L-type calcium current by intracellularly applied trypsin in guinea-pig ventricular myocytes. J Physiol 404:259–274

    Google Scholar 

  • Hess P, Tsien RW (1984) Mechanism of ion permeation through calcium channels. Nature 309:453–456

    Google Scholar 

  • Hille B (1994) Modulation of ion-channel function by G-protein-coupled receptors. Trends Neurosci 17:531–536

    Google Scholar 

  • Hockerman GH, Johnson BD, Abbott MR, Scheuer T, Catterall WA (1997a) Molecular determinants of high affinity phenylalkylamine block of L-type calcium channels in transmembrane segment IIIS6 and the pore region of the α1 subunit. J Biol Chem 272:18759–18765

    Google Scholar 

  • Hockerman GH, Johnson BD, Scheuer T, Catterall WA (1995) Molecular determinants of high affinity phenylalkylamine block of L-type calcium channels. J Biol Chem 270:22119–22122

    Google Scholar 

  • Hockerman GH, Peterson BZ, Sharp E, Tanada TN, Scheuer T, Catterall WA (1997b) Construction of a high-affinity receptor site for dihydropyridine agonists and antagonists by single amino acid substitutions in a non-L-type Ca2+ channel. Proc Natl Acad Sci USA 94:14906–14911

    Google Scholar 

  • Höfer G, Hohenthanner K, Baumgartner W, Groschner K, Klugbauer N, Hofmann F, Romanin C (1996) Intracellular Ca2+ inactivates L-type Ca2+ channels with a Hill coefficient of ≈1 and a Ki of ≈4 µM by reducing channels's open probability. Biophys J 73:1857–1865

    Google Scholar 

  • Hofmann F, Biel M, Flockerzi V (1994) Molecular basis for Ca2+ channel diversity. Annu Rev Neurosci 17:399–418

    Google Scholar 

  • Hu H, Marban E (1998) Isoform-specific inhibition of L-type calcium channels by dihydropyridines is independent of isoform-specific gating properties. Mol Pharmacol 53:902–907

    Google Scholar 

  • Hullin R, Singer-Lahat D, Freichel M, Biel M, Dascal N, Hofmann F, Flockerzi V (1992) Calcium channel ß subunit heterogeneity: functional expression of cloned cDNA from heart, aorta and brain. EMBO J 11:885–890

    Google Scholar 

  • Ito H, Klugbauer N, Hofmann F (1997) Transfer of the high affinity dihydropyridine sensitivity from L-type to non-L-type calcium channel. Mol Pharmacol 52:735–740

    Google Scholar 

  • Jay SD, Ellis SB, McCue AF, Williams ME, Vedvick TS, Harpold MM, Campbell KP (1990) Primary structure of the γ subunit of the DHP-sensitive calcium channel from skeletal muscle. Science 248:490–492

    Google Scholar 

  • Jeziorski MC, Greenberg RM, Clark KS, Anderson PAV (1998) Cloning and functional expression of a voltage-gated calcium channel α1 subunit from Jellyfish. J Biol Chem 273:22792–22799

    Google Scholar 

  • Johnson BD, Hockerman GH, Scheuer T, Catterall WA (1996) Distinct effects of mutations in transmembrane segment IVS6 on block of L-type calcium channels by structurally similar phenylalkylamines. Mol Pharm 50:1388–1400

    Google Scholar 

  • Johnson BD, Scheuer T, Catterall WA (1994) Voltage-dependent potentiation of L-type Ca2+ channels in skeletal muscle cells requires anchored cAMP-dependent protein kinase. Proc Natl Acad Sci USA 91:11492–11496

    Google Scholar 

  • Josephson IR, Varadi G (1996) The β subunit increases Ca2+ currents and gating charge movements of human cardiac L-type Ca2+ channels. Biophys J 70:1285–1293

    Google Scholar 

  • Jurkat-Rott K, Lehmann-Horn F, Elbaz A, Heine R, Gregg RG, Hogan K, Powers PA, Lapie P, Vale-Santos JE, Weissenbach J, Fontaine B (1994) A calcium channel mutation causing hypokalemic periodic paralysis. Hum Mol Gen 3:1415–1419

    Google Scholar 

  • Jurkat-Rott K, Uetz U, Pika-Hartlaub U, Powell J, Fontaine B, Melzer W, Lehmann-Horn F (1998) Calcium currents and transients of native and heterologously expressed mutant skeletal muscle DHP receptor α1 subunits (R528H) FEBS Lett 423:198–204

    Google Scholar 

  • Kalasz H, Watanabe T, Yabana H, Itagaki K, Naito K, Nakayama H, Schwartz A, Vaghy PL (1993) Identification of 1,4-dihydropyridine binding domains within the primary structure of the α1 subunit of the skeletal muscle L-type calcium channel. FEBS Lett 331:177–181

    Google Scholar 

  • Kamejama M, Hofmann F, Trautwein W (1985) On the mechanism of β-adrenergic regulation of the Ca channel on the guinea pig heart. Pflügers Arch 405:285–293

    Google Scholar 

  • Kamp TJ, Perez-Garcia MT, Marban E (1996) Enhancement of ionic current and charge movement by coexpression of calcium channel β1A subunit with α1C subunit in a human embryonic kidney cell line. J Physiol 492:89–96

    Google Scholar 

  • Kim DK, Catterall WA (1997) Ca2+-dependent and-independent interactions of the isoforms of the α1A subunit of brain Ca2+ channels with presynaptic SNARE proteins. Proc Natl Acad Sci USA 94:14782–14786

    Google Scholar 

  • Kim MS, Morii T, Sun LX, Imoto K, Mori Y (1993) Structural determinants of ion selectivity in brain calcium channel. FEBS Lett 318:145–148

    Google Scholar 

  • Kleppisch T, Pedersen K, Strübing C, Bosse-Doenecke E, Flockerzi V, Hofmann F, Hescheler J (1994) Double-pulse facilitation of smooth muscle α1 subunit Ca2+ channels expressed in CHO cells. EMBO J 13:2502–2507

    Google Scholar 

  • Klöckner U, Mikala G, Schwartz A, Varadi G (1995) Involvement of the carboxylterminal region of the α1 subunit in voltage-dependent inactivation of cardiac calcium channels. J Biol Chem 270:17306–17310

    Google Scholar 

  • Klöckner U, Mikala G, Schwartz A, Varadi G (1996) Molecular studies of the asymmetric pore structure of the human cardiac voltage-dependent Ca2+ channel. Conserved residue, Glu-1086, regulates proton-dependent ion permeation. J Biol Chem 271:22293–22296

    Google Scholar 

  • Klugbauer N, Lacinová L, Marais E, Hobom M, Hofmann F (1999a) Molecular diversity of the calcium channel α2δ subunit. J Neurosci 19:684–691

    Google Scholar 

  • Klugbauer N, Marais E, Lacinová L, Hofmann F (1999b) A T-type calcium channel from brain. Pflügers Arch (in press)

    Google Scholar 

  • Klugbauer N, Specht V, Dai S, Hofmann F (1999c) Cloning of new γ subunits. (submitted)

    Google Scholar 

  • Kraus RL, Sinnegger MJ, Glossmann H, Hering S, Striessnig J (1998) Familial hemiplegic migraine mutations change α1A Ca2+ channel kinetics. J Biol Chem 273:5586–5590

    Google Scholar 

  • Kuniyasu A, Itagaki K, Shibano T, Iino M, Kraft G, Schwartz A, Nakayama H (1998) Photochemical identification of transmembrane segment IVS6 as the binding region of semotiadil, a new modulator for the L-type voltage-dependent Ca2+ channel. J Biol Chem 273:4635–4641

    Google Scholar 

  • Kuo CC, Hess P (1993) Ion permeation in through the L-type Ca2+ channel in rat PC12 cells: two sets of ion binding sites in the pore. J Physiol 466:629–655

    Google Scholar 

  • Kurokawa J, Adachi-Akahane S, Nagao T (1997) 1,5-benzothiazepine binding domain is located on the extracellular side of the cardiac L-type Ca2+ channel. Mol Pharmacol 51:262–268

    Google Scholar 

  • Lacerda AE, Rampe D, Brown AM (1988) Effects of protein kinase C activators on cardiac Ca2+ channels. Nature 335:249–251

    Google Scholar 

  • Lacinová L, An RH, Hofmann F, Triggle D, Kass RS (1997) Mutational analysis of L-type Ca2+ channels reveals distinct regulatory sites for neutral and charged dihydropyridine (DHP) derivatives. Biophys J 72:A244

    Google Scholar 

  • Lacinová L, Hofmann F (1998) Isradipine interacts with the open state of the L-type calcium channel at high concentrations. Receptor and Channels 6:153–164

    Google Scholar 

  • Lacinová L, Klugbauer N, Hofmann F (1998) Inactivated states of α1Ca and α1Co splice variants of L-type calcium channels have different affinities for dihydropyridines. N-Sch Arch Pharmacol 358 Suppl 2:R693

    Google Scholar 

  • Lacinová L, Klugbauer N, Hofmann F (1999) Lack of modulation of the expressed calcium channel α1G subunit by α2δ subunits. J Physiol (in press)

    Google Scholar 

  • Lacinová L, Ludwig A, Bosse E, Flockerzi V, Hofmann F (1995) The block of the expressed L-type calcium channel is modulated by the ß3 subunit. FEBS Lett 373:103–107

    Google Scholar 

  • Lambert RC, Maulet Y, Mouton J, Beattie R, Volsen S, De Waard M, Feltz A (1997) T-type Ca2+ current properties are not modified by Ca2+ channel ß subunit depletion in nodosus ganglion neurons. J Neurosci 17:6621–668

    Google Scholar 

  • Lapie P, Goudet C, Nargeot J, Fontaine B, Lory P (1996) Electrophysiological properties of the hypokalaemic periodic paralysis mutation (R528H) of the skeletal muscle α1S subunit as expressed in mouse L cells. FEBS Lett 382:244–248

    Google Scholar 

  • Lee KS (1987) Potentiation of the calcium-channel currents of internally perfused mammalian heart cells by repetitive depolarization. Proc Natl Acad Sci USA 84:3941–3945

    Google Scholar 

  • Lee RY, Lobel L, Hengartner M, Horvitz HR, Avery L (1997) Mutations in the α1 subunit of an L-type voltage-activated Ca2+ channel cause myotonia in Caenorhabditis elegans. EMBO J 16:6066–6076

    Google Scholar 

  • Lerche H, Klugbauer N, Lehmann-Horn F, Hofmann F, Melzer W (1996) Expression and functional characterization of the cardiac L-type calcium channel carrying a skeletal muscle DHP-receptor mutation causing hypokalaemic periodic paralysis. Pflügers Arch 431:461–463

    Google Scholar 

  • Letts VA, Felix R, Biddlecome GH, Arikkath J, Mahaffey CL, Valenzuela A, Bartlett FS, Mori Y, Campbell KP, Frankel WN (1998) The mouse stargazer gene encodes a neuronal Ca2+-channel γ subunit. Nature Gen 19:340–347

    Google Scholar 

  • Leuranguer V, Bourinet E, Lory P, Nargeot J (1998) Antisense depletion of β-subunits fails to affect T-type calcium channels properties in a neuroblastoma cell line. Neuropharmacol 37:701–708

    Google Scholar 

  • Leveque C, el Far O, Martin-Moutot N, Sato K, Kato R, Takahashi M, Seagar MJ (1994) Purification of the N-type calcium channel associated with syntaxin and synaptotagmin. A complex implicated in synaptic vesicle exocytosis. J Biol Chem 269:6306–9312

    Google Scholar 

  • Leveque C, Pupier S, Marqueze B, Geslin L, Kataoka M, Takahashi M, De Waard M, Seagar M (1998) Interaction of cysteine string proteins with the α1A subunit of the P/Q-type calcium channel. J Biol Chem 273:13488–13492

    Google Scholar 

  • Liman ER, Hess P, Weaver F, Koren G (1991) Voltage-sensing residues in the S4 region of a mammalian K+ channel. Nature 35:752–756

    Google Scholar 

  • Liu H, De Waard M, Scott VES, Gurnett CA, Lennon VA, Campbell KP (1996) Identification of three subunits of the high affinity omega-conotoxin MVIIC-sensitive Ca2+ channel. J Biol Chem 271:13804–13810

    Google Scholar 

  • Lu X, Xu L, Meissner G (1994) Activation of the skeletal muscle calcium release channel by a cytoplasmic loop of the dihydropyridine receptor. J Biol Chem 269:6511–6516

    Google Scholar 

  • Lu X, Xu L, Meissner G (1995) Phosphorylation of dihydropyridine receptor II–III loop peptide regulates skeletal muscle calcium release channel function. Evidence for an essential role of the beta-OH group of Ser687. J Biol Chem 270:18459–18464

    Google Scholar 

  • Ludwig A, Flockerzi V, Hofmann F (1997) Regional expression and cellular localization of the α1 and ß subunit of high voltage-activated calcium channels in rat brain. J Neurosci 17:1339–1349

    Google Scholar 

  • Marrion NV, Tavalin SJ (1998) Selective activation of Ca2+-activated K+ channels by co-localized Ca2+ channels in hippocampal neurons. Nature 395:900–905

    Google Scholar 

  • Martin-Moutot N, Charvin N, Leveque C, Sato K, Nishiki T, Kozaki S, Takahashi M, Seagar M (1996) Interaction of SNARE complexes with P/Q-type calcium channels in rat cerebellar synaptosomes. J Biol Chem 271:6567–6570

    Google Scholar 

  • McDonough SI, Swartz KJ, Mintz IM, Boland LM, Bean BP (1996) Inhibition of calcium channels in rat central and peripheral neurons by omega-conotoxin MVIIC. J Neurosci 16:2612–2623

    Google Scholar 

  • McEnery MW, Copeland TD, Vance CL (1998) Altered expression and assembly of N-type calcium channel α1B and ß subunits in epileptic lethargic (lh/lh) mouse. J Biol Chem 273:21435–21438

    Google Scholar 

  • Meyers MB, Puri TS, Chien AJ, Gao TY, Hsu PH, Hosey MM, Fishman GI (1998) Sorcin associates with the pore-forming subunit of voltage-dependent L-type Ca2+ channels. J Biol Chem 273:18930–18935

    Google Scholar 

  • Meza U, Adams B (1998) G-protein-dependent facilitation of neuronal α1A, α1B and α1E Ca channels. J Neurosci 18:5240–5252

    Google Scholar 

  • Mikami A, Imoto K, Tanabe T, Niidome T, Mori Y, Takeshima H, Narumiya S, Numa S (1989) Primary structure and functional expression of the cardiac dihydropyridine-sensitive calcium channel. Nature 340:230–233

    Google Scholar 

  • Mitterdorfer J, Froschmayr M, Grabner M, Striessnig J, Glossmann H (1994) Calcium channels: the β-subunit increases the affinity of dihydropyridine and Ca2+ binding sites of the α1-subunit. FEBS Lett 352:141–145

    Google Scholar 

  • Mitterdorfer J, Sinnegger MJ, Grabner M, Striessnig J, Glossmann H (1995) Coordination of Ca2+ by the pore region glutamates is essential for high-affinity dihydropyridine binding to the cardiac Ca2+ channel α1 subunit. Biochemistry 34:9350–9355

    Google Scholar 

  • Morel N, Buryi V, Feron O, Gomez JP, Christen MO, Godfraind T (1998) The action of calcium channel blockers on recombinant L-type calcium channel α1-subunits Br J Pharmacol 125:1005–1012

    Google Scholar 

  • Mori Y, Friedrich T, Kim MS, Mikami A, Nakai J, Ruth P, Bosse E, Hofmann F, Flockerzi V, Furuichi T, Mikoshiba K, Imoto K, Tanabe T, Numa S (1991) Primary structure and functional expression from complementary DNA of a brain calcium channel. Nature 350:398–402

    Google Scholar 

  • Morrill JA, Brown Jr RH, Cannon SC (1998) Gating of the L-type Ca channel in himan skeletal myotubes: An activation defect caused by the hypokalemic periodic paralysis mutation R528H. J Neurosci 18:10320–10334

    Google Scholar 

  • Nakai J, Adams BA, Imoto K, Beam KG (1994) Critical roles of the S3 segment and S3–S4 linker of repeat I in activation of L-type calcium channels. Proc Natl Acad Sci USA 91:1014–1018

    Google Scholar 

  • Nakai J, Dirksen RT, Nguyen HT, Pessah IN, Beam KG, Allen PD (1996) Enhanced dihydropyridine receptor channel activity in the presence of ryanodine receptor. Nature 380:72–75

    Google Scholar 

  • Nakai J, Sekiguchi N, Rando TA, Allen PD, Beam KG (1998a) Two regions of the ryanodine receptor involved in coupling with L-type Ca2+ channels. J Biol Chem 273:13403–13406

    Google Scholar 

  • Nakai J, Tanabe T, Konno T, Adams B, Beam KG (1998b) Localization in the II-II loop of the dihydropyridine receptor of a sequence critical for excitation-contraction coupling. J Biol Chem 273:24983–24986

    Google Scholar 

  • Namkung Y, Smith SM, Lee SB, Skrypnyk NV, Kim H-L, Chin H, Scheller RH, Tsien RW, Shin H-S (1998) Targeted disruption of the Ca2+ channel ß3 subunit reduces N-and L-type Ca2+ channel activity and alters the voltage-dependent activation of P/Q-type Ca2+ channels in neurons. Proc Natl Acad Sci USA 95:12010–12015

    Google Scholar 

  • Neely A, Olcese R, Wei X, Birnbaumer L, Stefani E (1994) Ca2+-dependent inactivation of a cloned cardiac Ca2+ channel α1 subunit (α1C) expressed in Xenopus oocytes. Biophys J 66:1895–1903

    Google Scholar 

  • Neely A, Wei X, Olcese R, Birnbaumer L, Stefani E (1993) Potentiation by the β subunit of the ratio of the ionic current to the charge movement in the cardiac calcium channel. Science 262:575–578

    Google Scholar 

  • Neuhuber B, Gerster U, Doring F, Glossmann H, Tanabe T, Flucher BE (1998a) Association of calcium channel α1S and β1a subunits is required for the targeting of β1a but not of α1S into skeletal muscle triads. Proc Natl Acad Sci USA 95:5015–5020

    Google Scholar 

  • Neuhuber B, Gerster U, Mitterdorfer J, Glossmann H, Flucher BE (1998b) Differential effects of Ca2+ channel β1a and β2a subunits on complex formation with α1S and on current expression in tsA201 cells. J Biol Chem 273:9110–9118

    Google Scholar 

  • Niidome T, Kim MS, Friedrich T, Mori Y (1992) Molecular cloning and characterization of a novel calcium channel from rabbit brain. FEBS Lett 308:7–13

    Google Scholar 

  • Noebels JC, Sidmann RL (1979) Inherited epilepsy: spike-wave and focal motor seizures in the mutant mouse tottering. Science 204:1334–1336

    Google Scholar 

  • Olcese R, Qin N, Schneider T, Neely A, Wei X, Stefani E, Birnbaumer L (1994) The amino terminus of a calcium channel β subunit sets rates of channel inactivation independently of the subunit's effect on activation. Neuron 13:1433–1438

    Google Scholar 

  • Ophoff RA, Terwindt GM, Frants RR and Ferrari MD (1998) P/Q-type Ca2+ channel defects in migraine, ataxia and epilepsy. Trends Pharmacol Sci 19:121–127

    Google Scholar 

  • Ophoff RA, Terwindt GM, Vergouwe MN, Eijk RV, Oefner PJ, Hoffman SMG, Lamerdin JE, Mohrenweiser HW, Bulman DE, Ferrari M, Haan J, Lindhout D, Ommen G-JBV, Hofker MH, Ferrari MD, Frants RR (1996) Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell 87:543–552

    Google Scholar 

  • Osterrieder W, Brum G, Hescheler J, Trautwein W, Flockerzi V, Hofmann F (1982) Injection of subunits of cyclic AMP-dependent protein kinase into cardiac myocytes modulates Ca2+ current. Nature 298:576–578

    Google Scholar 

  • Page KM, Canti C, Stephens GJ, Berrow NS, Dolphin AC (1998) Identification of the amino terminus of neuronal Ca2+ channel α1 subunits α1B and α1E as an essential determinant of G-protein modulation. J Neurosci 18:4815–4824

    Google Scholar 

  • Papazian DM, Timpe LC, Jan YN, Jan LY (1991) Alteration of voltage-dependence of Shaker potassium channel by mutations in the S4 sequence. Nature 349:305–310

    Google Scholar 

  • Parent L, Gopalakrishnan M (1995) Glutamate substitution in repeat IV alters divalent and monovalent cation permeation in the heart Ca2+ channel. Biophys J 69:1801–1813

    Google Scholar 

  • Perets T, Blumenstein Y, Shistik E, Lotan I, Dascal N (1996) A potential site of functional modulation by protein kinase A in the cardiac Ca2+ channel α1C subunit. FEBS Lett 384:189–192

    Google Scholar 

  • Perez-Reyes E, Castellano A, Kim HS Bertrand P, Baggstrom E, Lacerda AE, Wei XY, Birnbaumer L (1992) Cloning and expression of a cardiac/brain β subunit of the L-type calcium channel. J Biol Chem 267:1792–1797

    Google Scholar 

  • Perez-Reyes E, Cribbs LL, Daud A, Lacerda AE, Barclay J, Williamson MP, Fox M, Rees M, Lee JH (1998a) Molecular characterization of a neuronal low-voltage-activated T-type calcium channel. Nature 391:896–900

    Google Scholar 

  • Perez-Reyes E, Cribbs LL, Daud A, Lacerda AE, Barclay J, Williamson MP, Fox M, Rees M, Lee JH (1998b) Molecular characterization of T-type calcium channels. In: Tsien RW, Clozel JP and Nargeot J (eds) Low-voltage-activated T-type calcium channels. Adis Int. Ltd., Chester, pp 290–307

    Google Scholar 

  • Perez-Reyes E, Yuan W, Wei X, Bers DM (1994) Regulation of the cloned L-type cardiac calcium channel by cyclic AMP-dependent protein kinase. FEBS Lett 342:119–123

    Google Scholar 

  • Peterson BZ, Catterall WA (1995) Calcium binding in the pore of L-type calcium channels modulates high affinity dihydropyridine binding. J Biol Chem 270:18201–18204

    Google Scholar 

  • Peterson BZ, Johnson BD, Hockerman GH, Acheson M, Scheuer T, Catterall WA (1997) Analysis of the dihydropyridine receptor site of L-type calcium channels by alanine-scanning mutagenesis. J Biol Chem 272:18752–18758

    Google Scholar 

  • Peterson BZ, Tanada TN, Catterall WA (1996) Molecular determinants of high affinity dihydropyridine binding in L-type calcium channels. J Biol Chem 271:5293–5286

    Google Scholar 

  • Pichler M, Cassidy TN, Reimer D, Haase H, Kraus R, Ostler D, Striessnig J (1997) β subunit heterogeneity in neuronal L-type Ca2+ channels. J Biol Chem 272:13877–13882

    Google Scholar 

  • Pietrobon D, Hess P (1990) Novel mechanism of voltage-dependent gating in L-type calcium channels. Nature 346:651–655

    Google Scholar 

  • Powers PA, Liu S, Hogan K, Gregg RG (1992) Skeletal muscle and brain isoforms of a ß-subunit of human voltage-dependent calcium channels are encoded by a single gene. J Biol Chem 267:22967–22972

    Google Scholar 

  • Powers PA, Liu S, Hogan K, Gregg RG (1993) Molecular characterization of the gene encoding the γ subunit of the human skeletal muscle 1,4-dihydropyridine-sensitive Ca2+ channel (CACNLG), cDNA sequence, gene structure, and chromosomal location. J Biol Chem 268:9275–9279

    Google Scholar 

  • Pragnell M, De Waard M, Mori Y, Tanabe T, Snutch TP, Campbell KP (1994) Calcium channel ß-subunit binds to a conserved motif in the I–II cytoplasmic linker of the α1 subunit. Nature 368:67–70

    Google Scholar 

  • Pragnell M, Sakamoto J, Jay SD, Campbell KP (1991) Cloning and tissue-specific expression of the brain calcium channel ß-subunit. FEBS Lett 291:253–258

    Google Scholar 

  • Ptacek LJ (1997) Channelopathies: ion channel disorders of muscle as a paradigm for paroxysmal disorders of the nervous system. Neuromuscular Disorders 7:250–255

    Google Scholar 

  • Ptacek LJ, Tawil R, Griggs RC, Engel AG, Layzer RB, Kwiecinski H, McManis PG, Santiago L, Moore M, Fouad G, Bradley P, Leppert MF (1994) Dihydropyridine receptor mutations cause hypokalemic periodic paralysis. Cell 77:863–868

    Google Scholar 

  • Qin N, Olcese R, Stefani E, Birnbaumer L (1998b) Modulation of human neuronal α1E-type calcium channel by α2δ-subunit. Am J Physiol 274:C1324–C1331

    Google Scholar 

  • Qin N, Platano D, Olcese R, Costantin JL, Stefani E, Birnbaumer L (1998a) Unique regulatory properties of the type 2a Ca2+ channel β subunit caused by palmitoylation. Proc Natl Acad Sci USA 95:4690–4695

    Google Scholar 

  • Qin N; Platano D, Olcese R, Stefani E, Birnbaumer L (1997) Direct interaction of Gßγ with a C-terminal Gßγ-binding domain of the Ca2+ channel α1 subunit is responsible for channel inhibition by G protein-coupled receptors. Proc Natl Acad Sci USA 94:8866–8871

    Google Scholar 

  • Randall AD, Tsien RW (1997) Contrasting biophysical and pharmacological properties of T-type and R-type calcium channels. Neuropharmacology 36:879–893

    Google Scholar 

  • Regulla S, Schneider T, Nastainczyk W, Meyer HE, Hofmann F (1991) Identification of the site of interaction of the dihydropyridine channel blockers nitrendipine and azidopine with the calcium-channel α1 subunit. EMBO J 10:45–49

    Google Scholar 

  • Ren D, Hall LM (1997) Functional expression and characterization of skeletal muscle dihydropyridine receptors in Xenopus oocytes. J Biol Chem 272:22393–22396

    Google Scholar 

  • Rettig J, Heinemann C, Ashery U, Sheng ZH, Yokoyama CT, Catterall WA, Neher E (1997) Alteration of Ca2+ dependence of neurotransmitter release by disruption of Ca2+ channel/syntaxin interaction. J Neurosci 17:6647–6656

    Google Scholar 

  • Rettig J, Sheng ZH, Kim DK, Hodson CD, Snutch TP, Catterall WA (1996) Isoform-specific interaction of the α1A subunits of brain Ca2+ channels with the presynaptic proteins syntaxin and SNAP-25. Proc Natl Acad Sci USA 93:7363–7368

    Google Scholar 

  • Röhrkasten A, Meyer H, Nastainczyk W, Sieber M, Hofmann F (1988) cAMP-dependent protein kinase rapidly phosphorylates Ser687 of the rabbit skeletal muscle receptor for calcium channel blockers. J Biol Chem 263:15325–15329

    Google Scholar 

  • Rosenberg RL, Chen XH (1991) Characterization and localization of two ion binding sites within the pore of cardiac L-type calcium channels. J Gen Physiol 97:1207–1225

    Google Scholar 

  • Rotman EI, Murphy BJ, Catterall WA (1995) Sites of selective cAMP-dependent phosphorylation of the L-type calcium channel α1 subunit from intact rabbit skeletal muscle myotubes. J Biol Chem 270:16371–16377

    Google Scholar 

  • Ruth P, Röhrkasten A, Biel M, Bosse E, Regulla S, Meyer HE, Flockerzi V, Hofmann F (1989) Primary structure of the ß subunit of the DHP-sensitive calcium channel from skeletal muscle. Science 245:1115–1118

    Google Scholar 

  • Sather WA, Tanabe T, Zhang JF, Mori Y, Adams ME, Tsien RW (1993) Distinctive biophysical and pharmacological properties of class A (BI) calcium channel α1 subunits. Neuron 11:291–303

    Google Scholar 

  • Schmid R, Seydl K, Baumgartner W, Groschner K, Romanin C (1995) Trypsin increases availability and open probability of cardiac L-type Ca2+ channels without affecting inactivation induced by Ca2+. Biophys J 69:1847–1857

    Google Scholar 

  • Schneider T, Regulla S, Hofmann F (1991) The Devapamil binding site of the purified skeletal muscle CaCB-receptor is modulated by micromolar and millimolar calcium. Eur J Biochem 200:245–253

    Google Scholar 

  • Schneider T, Wei X, Olcese R, Costantin JL, Neely A, Palade P, Perez-Reyes E, Qin N, Zhou J, Crawford GD, Smith RG, Appel SH, Stefani E, Birnbaumer L (1994) Molecular analysis and functional expression of the human type E neuronal Ca2+ channel α1 subunit. Receptors Channels 2:255–270

    Google Scholar 

  • Schuhmann K, Groschner K (1994) Protein kinase-C mediates dual modulation of L-type Ca2+ channels in human vascular smooth muscle. FEBS Lett 341:208–212

    Google Scholar 

  • Schuhmann K, Voelker C, Höfer GF, Plügelmeier H, Klugbauer N, Hofmann F, Romanin C, Groschner K (1997) Essential role of the β subunit in modulation of C class L-type Ca2+ channels by intracellular pH. FEBS Lett 408:75–80

    Google Scholar 

  • Schultz D, Mikala G, Yatani A, Engle DB, Iles DE, Segers B, Sinke RJ, Weghuis DO, Klockner U, Wakamori M, Wang J-J, Melvin D, Varadi G, Schwartz A (1993) Cloning, chromosomal localization, and functional expression of the α1 subunit of the L-type voltage-dependent calcium channel from normal human heart. Proc Natl Acad Sci USA 90:6228–6232

    Google Scholar 

  • Schuster A, Lacinová L, Klugbauer N, Ito H, Birnbaumer L, Hofmann F (1996) The IVS6 segment of the L-type calcium channel is critical for the action of dihydropyridines and phenylalkylamines. EMBO J 15:2365–2370

    Google Scholar 

  • Scott VE, De Waard M, Liu H, Gurnett CA, Venzke DP, Lennon VA, Campbell KP (1996) Beta subunit heterogeneity in N-type Ca2+ channels. J Biol Chem 271:3207–3212

    Google Scholar 

  • Sculptoreanu A, Rotman E, Takahashi M, Scheuer T, Catterall WA (1993a). Voltage-dependent potentiation of the activity of cardiac L-type calcium channel α1 subunit due to phosphorylation by cAMP-dependent protein kinase. Proc Natl Acad Sci USA 90:10135–10139

    Google Scholar 

  • Sculptoreanu A, Scheuer T, Catterall WA (1993b). Voltage-dependent potentiation of L-type Ca2+ channels due to phosphorylation by cAMP-dependent protein kinase. Nature 364:240–243

    Google Scholar 

  • Seino S, Chen L, Seino M, Blondel D, Takeda J, Johnson JH, Bell GI (1992). Cloning of the α1 subunit of a voltage-dependent calcium channel expressed in pancreatic ß-cells. Proc Natl Acad Sci USA 89:584–588

    Google Scholar 

  • Seisenberger C, Pfeifer A, Klugbauer N, Hofmann F (1998) Targeted disruption of the calcium channel α1c gene show a beating heart later than day 9.5 pc. N-Sch Arch Pharmacol 358:R164

    Google Scholar 

  • Seisenberger C. Welling A, Schuster A, Hofmann F (1995) Two stable cell lines for screening of calcium channel blockers. N-Sch Arch Pharmacol 352:662–669

    Google Scholar 

  • Sham JS, Cleemann L, Morad M (1995) Functional coupling of Ca2+ channels and ryanodine receptors in cardiac myocytes. Proc Natl Acad Sci USA 92:121–125

    Google Scholar 

  • Sheng ZH, Rettig J, Cook T, Catterall WA (1996) Calcium-dependent interaction of N-type calcium channels with the synaptic core complex. Nature 379:451–454

    Google Scholar 

  • Sheng ZH, Rettig J, Takahashi M, Catterall WA (1994) Identification of a syntaxinbinding site on N-type calcium channels. Neuron 13:1303–1313

    Google Scholar 

  • Sheng ZH, Yokoyama CT, Catterall WA (1997) Interaction of the synprint site of N-type Ca2+ channels with the C2B domain of synaptotagmin I. Proc Natl Acad Sci USA 94:5405–5410

    Google Scholar 

  • Shirokov R, Ferreira G, Yi J, Ríos E (1998) Inactivation of gating currents of L-type calcium channels. Specific role of the α2δ subunit. J Gen Physiol 111:807–823

    Google Scholar 

  • Shistik E, Ivanina T, Blumenstein Y, Dascal N (1998) Crucial role of N terminus in function of cardiac L-type Ca2+ channel and its modulation by protein kinase C. J Biol Chem 273:17901–17909

    Google Scholar 

  • Shistik E, Ivanina T, Puri T, Hosey M, Dascal N (1995) Ca2+ current enhancement by α2/δ and β subunits in Xenopus oocytes: contribution of changes in channel gating and α1 protein level. J Physiol 489:55–62

    Google Scholar 

  • Singer D, Biel M, Lotan I, Flockerzi V, Hofmann F, Dascal N (1991) The roles of the subunits in the function of the calcium channel. Science 253:1553–1557

    Google Scholar 

  • Singer-Lahat D, Gershon E, Lotan I, Hullin R, Biel M, Flockerzi V, Hofmann F, Dascal N (1992) Modulation of cardiac Ca2+ channels in Xenopus oocytes by protein kinase C. FEBS Lett 306:113–118

    Google Scholar 

  • Singer-Lahat D, Lotan I, Biel M, Flockerzi V, Hofmann F, Dascal N (1994) Cardiac calcium channels expressed in Xenopus oocytes are modulated by dephosphorylation but not by cAMP-dependent phosphorylation. Receptors Channels 2:215–226

    Google Scholar 

  • Sinnegger MJ, Wang Z, Grabner M, Hering S, Striessnig J, Glossmann H, Mitterdorfer J (1997) Nine L-type amino acid residues confer full 1,4-dihydropyridine sensitivity to the neuronal calcium channel α1A subunit. Role of L-type Met1188. J Biol Chem 272:27686–27693

    Google Scholar 

  • Sipos I, Jurkatt-Rott K, Harasztosi CS, Fontaine B, Kovacs L, Melzer W, Lehmann-Horn F (1995) Skeletal muscle DHP receptor mutations alter calcium currents in human hypokalaemic periodic paralysis myotubes. J Physiol 483:299–306

    Google Scholar 

  • Snutch TP, Tomlinson WJ, Leonard JP, Gilbert MM (1991) Distinct calcium channels are generated by alternative splicing and are differentially expressed in the mammalian CNS. Neuron 7:45–57

    Google Scholar 

  • Soldatov NM (1994) Genomic structure of human L-type Ca2+ channel. Genomics 22:77–87

    Google Scholar 

  • Soldatov NM, Oz M, O'Brien KA, Abernethy DR, Morad M (1998) Molecular determinants of L-type Ca2+ channel inactivation. Segment exchange analysis of the carboxyl-terminal cytoplasmic motif encoded by exons 40–42 of the human α1C subunit gene. J Biol Chem 273:957–963

    Google Scholar 

  • Soong TW, Stea A, Hodson CD, Dubel SJ, Vincent SR, Snutch TP (1993) Structure and functional expression of a member of the low voltage-activated calcium channel family. Science 260:1133–1136

    Google Scholar 

  • Bezprozvanny I, Scheller RH, Tsien RW (1995) Functional impact of syntaxin on gating of N-type and Q-type calcium channels. Nature 378:623–626

    Google Scholar 

  • Starr TVB, Prystay W, Snutch TP (1991) Primary structure of a calcium channel that is highly expressed in the rat cerebellum. Proc Natl Acad Sci USA 88:5621–5625

    Google Scholar 

  • Stea A, Tomlinson WJ, Soong TW, Bourinet E, Dubel SJ, Vincent SR, Snutch TP (1994) Localization and functional properties of a rat brain α1A calcium channel reflect similarities to neuronal Q-and P-type channels. Proc Natl Acad Sci USA 91:10576–10580

    Google Scholar 

  • Stefani A, Spadoni F, Bernardi G (1998) Gabapentin inhibits calcium currents in isolated rat brain neurons. Neuropharmacology 37:83–91

    Google Scholar 

  • Stephens GJ, Canti C, Page KM, Dolphin AC (1998) Role of domain I of neuronal Ca2+ channel α1 subunits in G protein modulation. J Physiol 509:163–169

    Google Scholar 

  • Striessnig J, Berger W, Glossmann H (1993) Molecular properties of voltage-dependent Ca2+ channels in excitable tissues. Cell Physiol Biochem 3:295–317

    Google Scholar 

  • Strom TM, Nyakatura G, Apfelstedt-Sylla E, Hellebrand H, Lorenz B, Weber BH, Wutz K, Gutwillinger N, Ruther K, Drescher B, Sauer C, Zrenner E, Meitinger T, Rosenthal A, Meindl A (1998) An L-type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness. Nature Genet 19:260–263

    Google Scholar 

  • Stühmer W, Conti F, Suzuki H, Wang XD, Noda M, Yahagi N, Kubo H, Numa S (1989) Structural parts involved in activation and inactivation of the sodium channel. Nature 339:597–603

    Google Scholar 

  • Südhof TC (1995) The synaptic vesicle cycle: a cascade of protein-protein interactions. Nature 375:645–653

    Google Scholar 

  • Südhof TC, Rizo J (1996) Synaptotagmins: C2-domain proteins that regulate membrane traffic. Neuron 17:379–388

    Google Scholar 

  • Suh-Kim H, Wei X, Klos A, Pan S, Ruth P, Flockerzi V, Hofmann F, Perez-Reyes E, Birnbaumer L (1996) Reconstitution of the skeletal muscle dihydropyridine receptor. Functional interaction among α1, ß, γ and α2δ subunits. Receptors Channels 4:217–225

    Google Scholar 

  • Tanabe T, Adams BA, Numa S, Beam KG (1991) Repeat I of the dihydropyridine receptor is critical in determining calcium channel activation kinetics. Nature 352:800–803

    Google Scholar 

  • Tanabe T, Beam KG, Adams BA, Niidome T, Numa S (1990) Regions of the skeletal muscle dihydropyridine receptor critical for excitation-contraction coupling. Nature 346:567–569

    Google Scholar 

  • Tanabe T, Takeshima H, Mikami A, Flockerzi V, Takahashi H, Kangawa K, Kojima M, Matsuo H, Hirose T, Numa S (1987) Primary structure of the receptor for calcium channel blockers from skeletal muscle. Nature 328:313–318

    Google Scholar 

  • Tang S, Mikala G, Bahinski A, Yatani A, Varadi G, Schwartz A (1993) Molecular localization of ion selectivity sites within the pore of a human L-type cardiac calcium channel. J Biol Chem 268:13026–13029

    Google Scholar 

  • Tareilus E, Roux M, Qin N, Olcese R, Zhou J, Stefani E, Birnbaumer L (1997) A Xenopus oocyte beta subunit: evidence for a role in the assembly/expression of voltage-gated calcium channels that is separate from its role as a regulatory subunit. Proc Natl Acad Sci USA 94:1703–1708

    Google Scholar 

  • Taylor CP, Gee NS, Su TZ, Kocsis JD, Welty DF, Brown JP, Dooley DJ, Boden P, Singh L (1998) A summary of mechanistic hypotheses of gabapentin pharmacology. Epilepsy Res 29:233–249

    Google Scholar 

  • Terwindt GM, Ophoff RA, Haan J, Sandkuijl LA, Frants RR, Ferrari MD (1998) Migraine, ataxia and epilepsy: a challenging spectrum of genetically determined calcium channelopathies. Eur J Hum Gen 6:297–307

    Google Scholar 

  • Tsien RW, Hess P, McCleskey EW, Rosenberg RL (1987) Calcium channels: mechanisms of selectivity, permeation, and block. Annu Rev Biophys Biophys Chem 16:265–90

    Google Scholar 

  • Vance CL, Begg CM, Lee WL, Haase H, Copeland TD, McEnery MW (1998) Differential expression and association of calcium channel α1B and β subunits during rat brain ontogeny. J Biol Chem 273:14495–14502

    Google Scholar 

  • Volsen SG, Day NC, McCormack AL, Smith W, Craig PJ, Beattie RE, Smith D, Ince PG, Shaw PJ, Ellis SB, Mayne N, Burnett JP, Gillespie A, Harpold MM (1997) The expression of voltage-dependent calcium channel β subunits in human cerebellum. Neurosci 8:161–174

    Google Scholar 

  • Walker D, Bichet D, Campbell KP, De Waard M (1998) A β4 isoform-specific interaction site in the carboxyl-terminal region of the voltage-dependent Ca2+ channel α1A subunit. J Biol Chem 273:2361–1367

    Google Scholar 

  • Wang Z, Grabner M, Berjukow S, Savchenko A, Glossmann H, Hering S (1995) Chimeric L-type Ca2+ channels expressed in Xenopus laevis oocytes reveal role of repeats III and IV in activation gating. J Physiol 486:131–137

    Google Scholar 

  • Watanabe T, Kalasz H, Yabana H, Kuniyasu A, Mershon J, Itagaki K, Vaghy PL, Naito K, Nakayama H, Schwartz A (1993) Azidobutyryl clentiazem, a new photoactivatable diltiazem analog, labels benzothiazepine binding sites in the α1 subunit of the skeletal muscle calcium channel. FEBS Lett 334:261–264

    Google Scholar 

  • Wei X, Neely A, Lacerda AE, Olcese R, Stefani E, Perez-Reyes E, Birnbaumer L (1994) Modification of Ca2+ channel activity by deletions at the carboxyl terminus of the cardiac α1 subunit. J Biol Chem 269:1635–1640

    Google Scholar 

  • Wei X, Neely A, Olcese R, Lang W, Stefani E, Birnbaumer L (1996) Increase in Ca2+ channel expression by deletions at the amino terminus of the cardiac α1C subunit. Receptors Channels 4:205–215

    Google Scholar 

  • Wei X, Pan S, Lang W, Kim H, Schneider T, Perez-Reyes E, Birnbaumer L (1995) Molecular determinants of cardiac Ca2+ channel pharmacology. Subunit requirement for the high affinity and allosteric regulation of dihydropyridine binding. J Biol Chem 270:27106–27111

    Google Scholar 

  • Wei XY, Perez-Reyes E, Lacerda AE, Schuster G, Brown AM, Birnbaumer, L (1991) Heterologous regulation of the cardiac Ca2+ channel α1 subunit by skeletal muscle β and γ subunits. J Biol Chem 266:21943–21947

    Google Scholar 

  • Welling A, Bosse E, Cavalié A, Bottlender R, Ludwig A, Nastainczyk W, Flockerzi V, Hofmann F (1993a) Stable coexpression of calcium channel α1, β and α2/δ subunits in a somatic cell line. J Physiol 471:749–765

    Google Scholar 

  • Welling A, Kwan YW, Bosse E, Flockerzi V, Hofmann F, Kass RS (1993b) Subunit-dependent modulation of recombinant L-type calcium channels: molecular basis for dihydropyridine tissue selectivity. Circ Res 73:974–980

    Google Scholar 

  • Welling A, Ludwig A, Zimmer S, Klugbauer N, Flockerzi V, Hofmann F (1997) Alternatively spliced IS6 segments of the α1C gene determine the tissue-specific dihydropyridine sensitivity of cardiac and vascular smooth muscle L-type calcium channels. Circ Res 81:526–532

    Google Scholar 

  • Williams ME, Brust PF, Feldman DH, Saraswathi P, Simerson S, Maroufi A, McCue AF, Velicelebi G, Ellis SB, Harpold MM (1992a) Structure and functional expression of an ε-conotoxin-sensitive human N-type calcium channel. Science 257:389–395

    Google Scholar 

  • Williams ME, Feldman DH, McCue AF, Brenner R, Velicelebi G, Ellis SB, Harpold MM (1992b) Structure and functional expression of α1, α2/δ and β subunits of a novel human neuronal calcium channel subtype. Neuron 8:71–84

    Google Scholar 

  • Williams ME, Marubio LM, Deal CR, Hans M, Brust PF, Philipson LH, Miller RJ, Johnson EC, Harpold MM, Ellis SB (1994) Structure and functional characterization of neuronal α1E calcium channel subtypes. J Biol Chem 269:22347–22357

    Google Scholar 

  • Wiser O, Bennett MK, Atlas D (1996) Functional interaction of syntaxin and SNAP-25 with voltage-sensitive L-and N-type Ca2+ channels. EMBO J 15:4100–4110

    Google Scholar 

  • Wiser O, Trus M, Tobi D, Halevi S, Giladi E, Atlas D (1996) The α2/δ subunit of voltage sensitive Ca2+ channels is a single transmembrane extracellular protein which is involved in regulated secretion. FEBS Lett 379:15–20

    Google Scholar 

  • Witcher DR, De Waard M, Liu-H, Pragnell M, Campbell KP (1995) Association of native Ca2+ channel β subunits with the α1 subunit interaction domain. J Biol Chem 270:18088–18093

    Google Scholar 

  • Wyatt CN, Page KM, Berrow NS, Brice NL, Dolphin AC (1998) The effect of overexpression of auxiliary Ca2+ channel subunits on native Ca2+ channel currents in undifferentiated mammalian NG108-15 cells. J Physiol 510:347–360

    Google Scholar 

  • Yamaguchi H, Hara M, Strobeck M, Fukasawa K, Schwartz A, Varadi G (1998) Multiple modulation pathways of calcium channel activity by a β subunit. Direct evidence of β subunit participation in membrane trafficking of the α1C subunit. J Biol Chem 273:19348–19356

    Google Scholar 

  • Yang J, Ellinor PT, Sather WA, Zhang JF, Tsien RW (1993) Molecular determinants of Ca2+ selectivity and ion permeation in L-type Ca2+ channels. Nature 366:158–161

    Google Scholar 

  • Yang J, Tsien RW (1993) Enhancement of N-and L-type calcium channel currents by protein kinase C in frog sympathetic neurons. Neuron 10:127–136

    Google Scholar 

  • Yatani A, Bahinski A, Mikala G, Yamamoto S, Schwartz A (1994) Single amino acid substitutions within the ion permeation pathway alter single-channel conductance of the human L-type cardiac Ca2+ channel. Circ Res 75:315–323

    Google Scholar 

  • Yokoyama CT, Sheng ZH, Catterall WA (1997) Phosphorylation of the synaptic protein interaction site on N-type calcium channels inhibits interactions with SNARE proteins. J Neurosci 17:6929–6938

    Google Scholar 

  • Yoshida A, Takahashi M, Nishimura S, Takeshima H, Kokubun S (1992) Cyclic AMP-dependent phosphorylation and regulation of the cardiac dihydropyridine-sensitive Ca channel. FEBS Lett 309:343–349

    Google Scholar 

  • You Y, Pelzer DJ, Pelzer S (1995) Trypsin and forskolin decrease the sensitivity of L-type calcium current to inhibition by cytoplasmic free calcium in guinea pig heart muscle cells. Biophys J 69:1838–1846

    Google Scholar 

  • Zamponi GW, Bourinet E, Nelson D, Nargeot J, Snutch TP (1997) Crosstalk between G proteins and protein kinase C mediated by the calcium channel α1 subunit. Nature 385:442–446

    Google Scholar 

  • Zhang JF, Ellinor PT, Aldrich RW, Tsien RW (1994) Molecular determinants of voltage-dependent inactivation in calcium channels. Nature 372:97–100

    Google Scholar 

  • Zhang JF, Ellinor PT, Aldrich RW, Tsien RW (1996) Multiple structural elements in voltage-dependent Ca2+ channels support their inhibition by G proteins. Neuron 17:991–1003

    Google Scholar 

  • Zhang JF, Randall AD, Ellinor PT, Horne WA, Sather WA, Tanabe T, Schwarz TL, Tsien RW (1993) Distinct pharmacology and kinetics of cloned neuronal Ca2+ channels and their possible counterparts in mammalian CNS neurons. Neuropharmacology 32, 1075–1088

    Google Scholar 

  • Zhou J, Olcese R, Qin N, Noceti F, Birnbaumer L, Stefani E (1997) Feedback inhibition of Ca2+ channels by Ca2+ depends on a short sequence of the C terminus that does not include the Ca2+-binding function of a motif with similarity to Ca2+-binding domains. Proc Natl Acad Sci USA 94:2301–2305

    Google Scholar 

  • Zhuchenko O, Bailey J, Bonnen P, Ashizawa T, Stockton DW, Amos C, Dobyns WB, Subramony SH, Zoghbi HY, Lee CC (1997) Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the α1A voltage-dependent calcium channel. Nat Genet 15:62–69

    Google Scholar 

  • Zong X, Hofmann F (1996) Ca2+-dependent inactivation of the class C L-type Ca2+ channel is a property of the α1 subunit. FEBS Letters 378:121–125

    Google Scholar 

  • Zong X, Schreieck J, Mehrke G, Welling A, Schuster A, Bosse E, Flockerzi V, Hofmann F (1995) On the regulation of the expressed L-type calcium channel by cAMP-dependent phosphorylation. Pflügers Arch 430:340–347

    Google Scholar 

  • Zühlke RD, Bouron A, Soldatov NM, Reuter H (1998) Ca2+ channel sensitivity towards the blocker isradipine is affected by alternative splicing of the human α1C subunit gene. FEBS Lett 427:220–224

    Google Scholar 

  • Zühlke RD, Reuter H (1998) Ca2+ sensitive inactivation of L-type Ca2+ channels depends on multiple cytoplasmic amino acid sequences of the α1C subunit. Proc Natl Acad Sci USA 95:3287–3294

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Pharmakologie und Toxikologie, Technische Universität München, Biedersteiner Straße 29, D-80802, München, Germany

    F. Hofmann, L. Lacinová & N. Klugbauer

Authors
  1. F. Hofmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. Lacinová
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. Klugbauer
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer-Verlag

About this chapter

Cite this chapter

Hofmann, F., Lacinová, L., Klugbauer, N. (1999). Voltage-dependent calcium channels: From structure to function. In: Reviews of Physiology, Biochemistry and Pharmacology, Volume 139. Reviews of Physiology, Biochemistry and Pharmacology, vol 139. Springer, Berlin, Heidelberg. https://doi.org/10.1007/BFb0033648

Download citation

  • DOI: https://doi.org/10.1007/BFb0033648

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-65694-4

  • Online ISBN: 978-3-540-49111-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation