![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
RA Lampe, PA Defeo, MD Davison, J Young, JL Herman, RC Spreen, MB Horn, TJ Mangano and RA Keith
Department of CNS Pharmacology, Zeneca Pharmaceuticals, Wilmington, Delaware 19897.
omega-Grammotoxin SIA, a peptidergic blocker of voltage-sensitive calcium channel (VSCC) responses, was purified from Grammostola spatulata (tarantula spider) venom by reverse phase high performance liquid chromatography. Protease-sensitive biological activity was monitored by determining the inhibition of K(+)-stimulated influx of 45Ca2+ into rat brain synaptosomes. Electrospray mass spectrometry indicated an average molecular mass of 4109.2 Da for the native peptide. Chemical reduction of omega-grammotoxin SIA indicated the presence of three disulfide bridges. Primary sequence data confirmed the existence of six cysteine residues and 36 residues in total, with an average theoretical molecular mass of 4109.7 Da for the amidated carboxyl-terminal species. The biological profile of omega-grammotoxin SIA indicated virtually complete blockade of presynaptic vertebrate N- type as well as P-type VSCC responses. Specifically, omega-grammotoxin SIA caused a concentration-dependent and virtually complete inhibition of K(+)-evoked influx of 45Ca2+ into either rat or chick brain synaptosomes. Similar inhibition profiles were generated for the inhibition of release of either D-[3H]aspartate or [3H]norepinephrine from rat hippocampal or [3H]norepinephrine from chick cortical brain slice preparations evoked by K+ depolarization. As reported earlier, omega-grammotoxin SIA did not inhibit 125I-omega-conotoxin GVIA, [3H]PN 200-110, or [3H]desmethoxyverapamil binding to neuronal membrane fragments. To our knowledge, omega-grammotoxin SIA is the first ligand identified to block putative N-channel function without displacement of 125I-omega-conotoxin GVIA. omega-Grammotoxin SIA thus represents a novel vertebrate VSCC antagonist that inhibits neuronal N- and P-type VSCC responses.
This article has been cited by other articles:
|
|
 |
|
  A. G. Garcia, A. M. Garcia-De-Diego, L. Gandia, R. Borges, and J. Garcia-Sancho Calcium signaling and exocytosis in adrenal chromaffin cells. Physiol Rev, October 1, 2006; 86(4): 1093 - 1131. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Wang, S. H. Roh, S. Kim, C. W. Lee, J. I. Kim, and K. J. Swartz Molecular Surface of Tarantula Toxins Interacting with Voltage Sensors in Kv Channels J. Gen. Physiol., March 29, 2004; 123(4): 455 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Brown, L. L. Lynch, T. L. Haley, and R. Arsanjani Pseudechetoxin Binds to the Pore Turret of Cyclic Nucleotide-gated Ion Channels J. Gen. Physiol., November 24, 2003; 122(6): 749 - 760. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Escoubas, C. Bernard, G. Lambeau, M. Lazdunski, and H. Darbon Recombinant production and solution structure of PcTx1, the specific peptide inhibitor of ASIC1a proton-gated cation channels Protein Sci., July 1, 2003; 12(7): 1332 - 1343. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Oswald, T. M. Suchyna, R. McFeeters, P. Gottlieb, and F. Sachs Solution Structure of Peptide Toxins That Block Mechanosensitive Ion Channels J. Biol. Chem., September 6, 2002; 277(37): 34443 - 34450. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Escoubas, S. Diochot, M.-L. Celerier, T. Nakajima, and M. Lazdunski Novel Tarantula Toxins for Subtypes of Voltage-Dependent Potassium Channels in the Kv2 and Kv4 Subfamilies Mol. Pharmacol., July 1, 2002; 62(1): 48 - 57. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Sidach and I. M. Mintz Kurtoxin, A Gating Modifier of Neuronal High- and Low-Threshold Ca Channels J. Neurosci., March 15, 2002; 22(6): 2023 - 2034. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. I. McDonough, L. M. Boland, I. M. Mintz, and B. P. Bean Interactions among Toxins That Inhibit N-type and P-type Calcium Channels J. Gen. Physiol., March 12, 2002; 119(4): 313 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Li-Smerin and K. J. Swartz Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels PNAS, July 21, 1998; 95(15): 8585 - 8589. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. I. McDonough, R. A. Lampe, R. A. Keith, and B. P. Bean Voltage-Dependent Inhibition of N- and P-Type Calcium Channels by the Peptide Toxin omega -Grammotoxin-SIA Mol. Pharmacol., December 1, 1997; 52(6): 1095 - 1104. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. Fujii, K. Kameyama, M. Hosono, Y. Hayashi, and K. Kitamura Effect of Cilnidipine, a Novel Dihydropyridine Ca++-channel antagonist, on N-type Ca++ Channel in Rat Dorsal Root Ganglion Neurons J. Pharmacol. Exp. Ther., March 1, 1997; 280(3): 1184 - 1191. [Abstract] [Full Text]
|
|
|
|
|
|
M. C. Sanguinetti, J. H. Johnson, L. G. Hammerland, P. R. Kelbaugh, R. A. Volkmann, N. A. Saccomano, and A. L. Mueller Heteropodatoxins: Peptides Isolated from Spider Venom that Block Kv4.2 Potassium Channels Mol. Pharmacol., March 1, 1997; 51(3): 491 - 498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Escoubas, J. R. De Weille, A. Lecoq, S. Diochot, R. Waldmann, G. Champigny, D. Moinier, A. Menez, and M. Lazdunski Isolation of a Tarantula Toxin Specific for a Class of Proton-gated Na+ Channels J. Biol. Chem., August 11, 2000; 275(33): 25116 - 25121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-P. Feng, J. Hamid, C. Doering, G. M. Bosey, T. P. Snutch, and G. W. Zamponi Residue Gly1326 of the N-type Calcium Channel alpha 1B Subunit Controls Reversibility of omega -Conotoxin GVIA and MVIIA Block J. Biol. Chem., May 4, 2001; 276(19): 15728 - 15735. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
