![[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}
|
|
|
|
|
||
J Snyders, KM Knoth, SL Roberds and MM Tamkun
Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232-2171.
The interaction of quinidine with a cloned human cardiac potassium channel (HK2) expressed in a stable mouse L cell line was studied using the whole-cell tight-seal voltage-clamp technique. Quinidine (20 microM) did not affect the initial sigmoidal activation time course of the current. However, it reduced the peak current and induced a subsequent decline, with a time constant of 8.2 +/- 0.8 msec, to 28 +/- 6% of control (at +60 mV). The concentration dependence of HK2 block at +60 mV yielded an apparent KD of 6 microM and a Hill coefficient of 0.9. The degree of block was voltage dependent. Block increased from 0.60 +/- 0.09 at 0 mV to 0.72 +/- 0.06 at +60 mV with 20 microM quinidine and from 0.39 +/- 0.20 to 0.48 +/- 0.16 with 6 microM. Paired analysis in seven experiments with 20 microM quinidine indicated that the voltage-dependent increase in block was significant (difference, 12 +/- 4%; p less than 0.001). This voltage dependence was described by an equivalent electrical distance delta of 0.19 +/- 0.02, which suggested that at the binding site quinidine experienced 19% of the applied transmembrane electrical field, referenced to the inner surface. Quinidine reduced the tail current amplitude and slowed the time course relative to control, resulting in a "crossover" phenomenon. These data indicate that 1) the charged form of quinidine blocks the HK2 channel after it opens, 2) binding occurs within the transmembrane electrical field (probably in or near the ion permeation pathway), and 3) unbinding is required before the channel can close.
This article has been cited by other articles:
|
|
 |
|
  M. Ander, V. B. Luzhkov, and J. Aqvist Ligand Binding to the Voltage-Gated Kv1.5 Potassium Channel in the Open State Docking and Computer Simulations of a Homology Model Biophys. J., February 1, 2008; 94(3): 820 - 831. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Eldstrom, Z. Wang, H. Xu, M. Pourrier, A. Ezrin, K. Gibson, and D. Fedida The Molecular Basis of High-Affinity Binding of the Antiarrhythmic Compound Vernakalant (RSD1235) to Kv1.5 Channels Mol. Pharmacol., December 1, 2007; 72(6): 1522 - 1534. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Kim, H. S. Ahn, B. H. Choi, H.-J. Jang, M.-J. Kim, D.-J. Rhie, S.-H. Yoon, Y.-H. Jo, M.-S. Kim, K.-W. Sung, et al. Open Channel Block of A-Type, Kv4.3, and Delayed Rectifier K+ Channels, Kv1.3 and Kv3.1, by Sibutramine J. Pharmacol. Exp. Ther., May 1, 2007; 321(2): 753 - 762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Decher, P. Kumar, T. Gonzalez, B. Pirard, and M. C. Sanguinetti Binding Site of a Novel Kv1.5 Blocker: A "Foot in the Door" against Atrial Fibrillation Mol. Pharmacol., October 1, 2006; 70(4): 1204 - 1211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Beekwilder, G. Th.H. van Kempen, R. J. van den Berg, and D. L. Ypey The Local Anesthetic Butamben Inhibits and Accelerates Low-Voltage Activated T-Type Currents in Small Sensory Neurons Anesth. Analg., January 1, 2006; 102(1): 141 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. H. Choi, J.-A. Park, K.-R. Kim, G.-I. Lee, Y.-T. Lee, H. Choe, S.-H. Ko, M.-H. Kim, Y.-H. Seo, and Y.-G. Kwak Direct block of cloned hKv1.5 channel by cytochalasins, actin-disrupting agents Am J Physiol Cell Physiol, August 1, 2005; 289(2): C425 - C436. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-Y. Choi, Y.-S. Koh, and S.-H. Jo Inhibition of Human ether-a-go-go-Related Gene K+ Channel and IKr of Guinea Pig Cardiomyocytes by Antipsychotic Drug Trifluoperazine J. Pharmacol. Exp. Ther., May 1, 2005; 313(2): 888 - 895. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Cruikshank, M. Hopperstad, M. Younger, B. W. Connors, D. C. Spray, and M. Srinivas Potent block of Cx36 and Cx50 gap junction channels by mefloquine PNAS, August 17, 2004; 101(33): 12364 - 12369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Tamargo, R. Caballero, R. Gomez, C. Valenzuela, and E. Delpon Pharmacology of cardiac potassium channels Cardiovasc Res, April 1, 2004; 62(1): 9 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Decher, B. Pirard, F. Bundis, S. Peukert, K.-H. Baringhaus, A. E. Busch, K. Steinmeyer, and M. C. Sanguinetti Molecular Basis for Kv1.5 Channel Block: CONSERVATION OF DRUG BINDING SITES AMONG VOLTAGE-GATED K+ CHANNELS J. Biol. Chem., January 2, 2004; 279(1): 394 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Appel, Z. Liu, M. A. McElvain, and M. S. Brodie Ethanol Excitation of Dopaminergic Ventral Tegmental Area Neurons Is Blocked by Quinidine J. Pharmacol. Exp. Ther., August 1, 2003; 306(2): 437 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Sanchez-Chapula, T. Ferrer, R. A. Navarro-Polanco, and M. C. Sanguinetti Voltage-Dependent Profile of Human Ether-a-go-go-Related Gene Channel Block Is Influenced by a Single Residue in the S6 Transmembrane Domain Mol. Pharmacol., May 1, 2003; 63(5): 1051 - 1058. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Madeja, T. Leicher, P. Friederich, M. A. Punke, W. Haverkamp, U. Musshoff, G. Breithardt, and E.-J. Speckmann Molecular Site of Action of the Antiarrhythmic Drug Propafenone at the Voltage-Operated Potassium Channel Kv2.1 Mol. Pharmacol., March 1, 2003; 63(3): 547 - 556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Choe, Y.-K. Lee, Y.-T. Lee, H. Choe, S.-H. Ko, C.-U. Joo, M.-H. Kim, G.-S. Kim, J.-S. Eun, J.-H. Kim, et al. Papaverine Blocks hKv1.5 Channel Current and Human Atrial Ultrarapid Delayed Rectifier K+ Currents J. Pharmacol. Exp. Ther., February 1, 2003; 304(2): 706 - 712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Gonzalez, R. Navarro-Polanco, C. Arias, R. Caballero, I. Moreno, E. Delpon, J. Tamargo, M. M. Tamkun, and C. Valenzuela Assembly with the Kvbeta 1.3 Subunit Modulates Drug Block of hKv1.5 Channels Mol. Pharmacol., December 1, 2002; 62(6): 1456 - 1463. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. G. Tsushima, J. E. Kelly, and J. A. Wasserstrom Subconductance Activity Induced by Quinidine and Quinidinium in Purified Cardiac Sarcoplasmic Reticulum Calcium Release Channels J. Pharmacol. Exp. Ther., May 1, 2002; 301(2): 729 - 737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Srinivas, M. G. Hopperstad, and D. C. Spray Quinine blocks specific gap junction channel subtypes PNAS, September 4, 2001; (2001) 191206198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zhang, S. Rajamani, Y. Chen, Q. Gong, Y. Rong, Z. Zhou, A. Ruoho, and C. T. January Cocaine Blocks HERG, but Not KvLQT1+minK, Potassium Channels Mol. Pharmacol., April 16, 2001; 59(5): 1069 - 1076. [Abstract] [Full Text]
|
|
|
|
|
|
J. A. Sánchez-Chapula, E. Salinas-Stefanon, J. Torres-Jácome, D. E. Benavides-Haro, and R. A. Navarro-Polanco Blockade of Currents by the Antimalarial Drug Chloroquine in Feline Ventricular Myocytes J. Pharmacol. Exp. Ther., April 1, 2001; 297(1): 437 - 445. [Abstract] [Full Text]
|
|
|
|
|
|
L. Perchenet and O. Clément-Chomienne Characterization of Mibefradil Block of the Human Heart Delayed Rectifier hKv1.5 J. Pharmacol. Exp. Ther., November 1, 2000; 295(2): 771 - 778. [Abstract] [Full Text]
|
|
|
|
|
|
I. C.-H. Yang, M. W. Scherz, A. Bahinski, P. B. Bennett, and K. T. Murray Stereoselective Interactions of the Enantiomers of Chromanol 293B with Human Voltage-Gated Potassium Channels J. Pharmacol. Exp. Ther., September 1, 2000; 294(3): 955 - 962. [Abstract] [Full Text]
|
|
|
|
 |
|
 J C Hancox, K C R Patel, and J V Jones Antiarrhythmics---from cell to clinic: past, present, and future Heart, July 1, 2000; 84(1): 14 - 24. [Full Text] [PDF]
|
|
|
|
|
|
B. H. Choi, J.-S. Choi, S.-W. Jeong, S. J. Hahn, S. H. Yoon, Y.-H. Jo, and M.-S. Kim Direct Block by Bisindolylmaleimide of Rat Kv1.5 Expressed in Chinese Hamster Ovary Cells J. Pharmacol. Exp. Ther., May 1, 2000; 293(2): 634 - 640. [Abstract] [Full Text]
|
|
|
|
|
|
L. Yue, J. L. Feng, Z. Wang, and S. Nattel Effects of ambasilide, quinidine, flecainide and verapamil on ultra-rapid delayed rectifier potassium currents in canine atrial myocytes Cardiovasc Res, April 1, 2000; 46(1): 151 - 161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-S. Choi, S. J. Hahn, D.-J. Rhie, S.-H. Yoon, Y.-H. Jo, and M.-S. Kim Mechanism of Fluoxetine Block of Cloned Voltage-Activated Potassium Channel Kv1.3 J. Pharmacol. Exp. Ther., October 1, 1999; 291(1): 1 - 6. [Abstract] [Full Text]
|
|
|
|
|
|
J. A. Sanchez-Chapula Mechanism of Transient Outward K+ Channel Block by Disopyramide J. Pharmacol. Exp. Ther., August 1, 1999; 290(2): 515 - 523. [Abstract] [Full Text]
|
|
|
|
|
|
R. C. Hogg, C. Trequattrini, L. Catacuzzeno, A. Petris, F. Franciolini, and D. J. Adams Mechanisms of Verapamil Inhibition of Action Potential Firing in Rat Intracardiac Ganglion Neurons J. Pharmacol. Exp. Ther., June 1, 1999; 289(3): 1502 - 1508. [Abstract] [Full Text]
|
|
|
|
|
|
D. J Snyders Structure and function of cardiac potassium channels Cardiovasc Res, May 1, 1999; 42(2): 377 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Franqueza, C. Valenzuela, J. Eck, M.M. Tamkun, J. Tamargo, and D.J. Snyders Functional expression of an inactivating potassium channel (Kv4.3) in a mammalian cell line Cardiovasc Res, January 1, 1999; 41(1): 212 - 219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Longobardo, E. Delpón, R. Caballero, J. Tamargo, and C. Valenzuela Structural Determinants of Potency and Stereoselective Block of hKv1.5 Channels Induced by Local Anesthetics Mol. Pharmacol., July 1, 1998; 54(1): 162 - 169. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. Courtemanche, R. J. Ramirez, and S. Nattel Ionic mechanisms underlying human atrial action potential properties: insights from a mathematical model Am J Physiol Heart Circ Physiol, July 1, 1998; 275(1): H301 - H321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nattel Experimental evidence for proarrhythmic mechanisms of antiarrhythmic drugs Cardiovasc Res, March 1, 1998; 37(3): 567 - 577. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Grace and A. J. Camm Quinidine N. Engl. J. Med., January 1, 1998; 338(1): 35 - 45. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Toyama, K. Kamiya, J. Cheng, J.-K. Lee, R. Suzuki, and I. Kodama Vesnarinone Prolongs Action Potential Duration Without Reverse Frequency Dependence in Rabbit Ventricular Muscle by Blocking the Delayed Rectifier K+ Current Circulation, November 18, 1997; 96(10): 3696 - 3703. [Abstract] [Full Text]
|
|
|
|
|
|
A. M. Choy, C. C. Lang, D. M. Chomsky, G. H. Rayos, J. R. Wilson, and D. M. Roden Normalization of Acquired QT Prolongation in Humans by Intravenous Potassium Circulation, October 7, 1997; 96(7): 2149 - 2154. [Abstract] [Full Text]
|
|
|
|
|
|
E. Delpon, C. Valenzuela, P. Gay, L. Franqueza, D. J Snyders, and J. Tamargo Block of human cardiac Kv1.5 channels by loratadine: voltage-, time- and use-dependent block at concentrations above therapeutic levels Cardiovasc Res, August 1, 1997; 35(2): 341 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zhang, J. W. Anderson, and D. Fedida J. Pharmacol. Exp. Ther., June 1, 1997; 281(3): 1247 - 1256. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. Feng, B. Wible, G.-R. Li, Z. Wang, and S. Nattel Antisense Oligodeoxynucleotides Directed Against Kv1.5 mRNA Specifically Inhibit Ultrarapid Delayed Rectifier K+ Current in Cultured Adult Human Atrial Myocytes Circ. Res., April 19, 1997; 80(4): 572 - 579. [Abstract] [Full Text]
|
|
|
|
|
|
X. F. Deng, S. Mulay, S. Chemtob, and D. R. Varma Mechanisms of the Atrium-Specific Positive Inotropic Activities of Quinidine- and Atropine-Like Agents in Rats J. Pharmacol. Exp. Ther., April 1, 1997; 281(1): 322 - 329. [Abstract] [Full Text]
|
|
|
|
|
|
T. Yang, D. J. Snyders, and D. M. Roden Inhibition of Cardiac Potassium Currents by the Vesnarinone Analog OPC-18790: Comparison with Quinidine and Dofetilide J. Pharmacol. Exp. Ther., March 1, 1997; 280(3): 1170 - 1175. [Abstract] [Full Text]
|
|
|
|
|
|
L. Fananapazir, D. Packer, and E. N. Prystowsky Differential Effects of Changes in Local Myocardial Refractoriness on Atrialand Ventricular Latency Circulation, September 15, 1996; 94(6): 1364 - 1371. [Abstract] [Full Text]
|
|
|
|
|
|
S. W. Yeola, T. C. Rich, V. N. Uebele, M. M. Tamkun, and D. J. Snyders Molecular Analysis of a Binding Site for Quinidine in a Human Cardiac Delayed Rectifier K+ Channel : Role of S6 in Antiarrhythmic Drug Binding Circ. Res., June 1, 1996; 78(6): 1105 - 1114. [Abstract] [Full Text]
|
|
|
|
|
|
T. Yang and D. M. Roden Extracellular Potassium Modulation of Drug Block of IKr : Implications for Torsade de Pointes and Reverse Use-Dependence Circulation, February 1, 1996; 93(3): 407 - 411. [Abstract] [Full Text]
|
|
|
|
|
|
D. J. Snyders and S. W. Yeola Determinants of Antiarrhythmic Drug Action : Electrostatic and Hydrophobic Components of Block of the Human Cardiac hKv1.5 Channel Circ. Res., September 1, 1995; 77(3): 575 - 583. [Abstract] [Full Text]
|
|
|
|
|
|
E. S. Levitan, R. Gealy, J. S. Trimmer, and K. Takimoto Membrane Depolarization Inhibits Kv1.5 Voltage-gated K[IMAGE] Channel Gene Transcription and Protein Expression in Pituitary Cells J. Biol. Chem., March 17, 1995; 270(11): 6036 - 6041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yang, D. J. Snyders, and D. M. Roden Ibutilide, a Methanesulfonanilide Antiarrhythmic, Is a Potent Blocker of the Rapidly Activating Delayed Rectifier K+ Current (IKr) in AT-1 Cells : Concentration-, Time-, Voltage-, and Use-Dependent Effects Circulation, March 15, 1995; 91(6): 1799 - 1806. [Abstract] [Full Text]
|
|
|
|
|
|
E. Delpon, C. Valenzuela, O. Perez, O. Casis, and J. Tamargo Propafenone Preferentially Blocks the Rapidly Activating Component of Delayed Rectifier K+ Current in Guinea Pig Ventricular Myocytes : Voltage-Independent and Time-Dependent Block of the Slowly Activating Component Circ. Res., February 1, 1995; 76(2): 223 - 235. [Abstract] [Full Text]
|
|
|
|
|
|
J. J. Salata, N. K. Jurkiewicz, A. A. Wallace, R. F. Stupienski III, P. J. Guinosso Jr, and J. J. Lynch Jr Cardiac Electrophysiological Actions of the Histamine H1-Receptor Antagonists Astemizole and Terfenadine Compared With Chlorpheniramine and Pyrilamine Circ. Res., January 1, 1995; 76(1): 110 - 119. [Abstract] [Full Text]
|
|
|
|
|
|
J. R. Martens, N. Sakamoto, S. A. Sullivan, T. D. Grobaski, and M. M. Tamkun Isoform-specific Localization of Voltage-gated K+ Channels to Distinct Lipid Raft Populations. TARGETING OF Kv1.5 TO CAVEOLAE J. Biol. Chem., March 9, 2001; 276(11): 8409 - 8414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Srinivas, M. G. Hopperstad, and D. C. Spray Quinine blocks specific gap junction channel subtypes PNAS, September 11, 2001; 98(19): 10942 - 10947. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
