© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Structure and function of cardiac potassium channels
Department of Molecular Biophysics, Physiology and Pharmacology (VIB), Department of Biochemistry (UIA) University of Antwerp, Universiteitsplein 1 – T4.21, B-2610 Antwerp, Belgium
dsnyders{at}uia.ua.ac.be
* Tel.: +32-3-820-2335; fax: +32-3-820-2541
Recent advances in molecular biology have had a major impact on our understanding of the biophysical and molecular properties of ion channels. This review is focused on cardiac potassium channels which, in general, serve to control and limit cardiac excitability. Approximately 60 K+ channel subunits have been cloned to date. The (evolutionary) oldest potassium channel subunits consist of two transmembrane (Tm) segments with an intervening pore-loop (P). Channels formed by four 2Tm–1P subunits generally function as inwardly rectifying K+-selective channels (KirX.Y): they conduct substantial current near the resting potential but carry little or no current at depolarized potentials. The inward rectifier IK1 and the ligand-gated KATP and KACh channels are composed of such subunits. The second major class of K+ channel subunits consists of six transmembrane segments (S1–S6). The S5–P–S6 section resembles the 2Tm–1P subunit, and the additional membrane-spanning segments (especially the charged S4 segment) endow these 6Tm–1P channels with voltage-dependent gating. For both major families, four subunits assemble into a homo- or heterotetrameric channel, subject to specific subunit–subunit interactions. The 6Tm–1P channels are closed at the resting potential, but activate at different rates upon depolarization to carry sustained or transient outward currents (the latter due to inactivation by different mechanisms). Cardiac cells typically display at least one transient outward current and several delayed rectifiers to control the duration of the action potential. The molecular basis for each of these currents is formed by subunits that belong to different Kvx.y subfamilies and alternative splicing can contribute further to the diversity in native cells. These subunits display distinct pharmacological properties and drug-binding sites have been identified. Additional subunits have evolved by concatenation of two 2Tm–1P subunits (4Tm–2P); dimers of such subunits yield voltage-independent leak channels. A special class of 6Tm–1P subunits encodes the ‘funny’ pacemaker current which activates upon hyperpolarization and carries both Na+ and K+ ions. The regional heterogeneity of K+ currents and action potential duration is explained by the heterogeneity of subunit expression, and significant changes in expression occur in cardiac disease, most frequently a reduction. This electrical remodelling may also be important for novel antiarrhythmic therapeutic strategies. The recent crystallization of a 2Tm–1P channel enhances the outlook for more refined molecular approaches.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. F. McBride The Emerging Role of Antiarrhythmic Compounds With Atrial Selectivity in the Management of Atrial Fibrillation J. Clin. Pharmacol., March 1, 2009; 49(3): 258 - 267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Tafreshi and J. Rowles A Review of the Investigational Antiarrhythmic Agent Dronedarone Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2007; 12(1): 15 - 26. [Abstract] [PDF]
|
|
|
|
 |
|
 M. A.G. van der Heyden, T. J.M. Wijnhoven, and T. Opthof Molecular aspects of adrenergic modulation of the transient outward current Cardiovasc Res, August 1, 2006; 71(3): 430 - 442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Hansen, T. G. Diness, T. Christ, J. Demnitz, U. Ravens, S.-P. Olesen, and M. Grunnet Activation of Human ether-a-go-go-Related Gene Potassium Channels by the Diphenylurea 1,3-Bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643) Mol. Pharmacol., January 1, 2006; 69(1): 266 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Hu, S. V. P. Jones, and W. H. Dillmann Effects of hyperthyroidism on delayed rectifier K+ currents in left and right murine atria Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1448 - H1455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Herrera, A. Mamarbachi, M. Simoes, L. Parent, R. Sauve, Z. Wang, and S. Nattel A Single Residue in the S6 Transmembrane Domain Governs the Differential Flecainide Sensitivity of Voltage-Gated Potassium Channels Mol. Pharmacol., August 1, 2005; 68(2): 305 - 316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. M. Choisy, J. C. Hancox, L. A. Arberry, A. M. Reynolds, M. J. Shattock, and A. F. James Evidence for a Novel K+ Channel Modulated by {alpha}1A-Adrenoceptors in Cardiac Myocytes Mol. Pharmacol., September 1, 2004; 66(3): 735 - 748. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. C. Ott, S. Berjukow, R. Marksteiner, E. Margreiter, G. Bock, G. Laufer, and S. Hering On the fate of skeletal myoblasts in a cardiac environment: down-regulation of voltage-gated ion channels J. Physiol., August 1, 2004; 558(3): 793 - 805. [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]
|
|
|
|
 |
|
 G. Barreiro, C. R. W. Guimaraes, and R. B. de Alencastro Potential of mean force calculations on an L-type calcium channel model Protein Eng. Des. Sel., March 1, 2003; 16(3): 209 - 215. [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]
|
|
|
|
 |
|
 M. R. Gralinski The Dog's Role in the Preclinical Assessment of QT Interval Prolongation Toxicol Pathol, January 1, 2003; 31(1_suppl): 11 - 16. [Abstract] [PDF]
|
|
|
|
|
|
R. Rajashree, J. C. Koster, K. P. Markova, C. G. Nichols, and P. A. Hofmann Contractility and ischemic response of hearts from transgenic mice with altered sarcolemmal KATP channels Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H584 - H590. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Vornanen, A. Ryokkynen, and A. Nurmi Temperature-dependent expression of sarcolemmal K+ currents in rainbow trout atrial and ventricular myocytes Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2002; 282(4): R1191 - R1199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Lu, M. P Mahaut-Smith, A. Varghese, C. L-H Huang, P. R Kemp, and J. I Vandenberg Effects of premature stimulation on HERG K+ channels J. Physiol., December 15, 2001; 537(3): 843 - 851. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. M. Wilde and D. M. Roden Predicting the Long-QT Genotype From Clinical Data : From Sense to Science Circulation, December 5, 2000; 102(23): 2796 - 2798. [Full Text] [PDF]
|
|
|
|
 |
|
 C.-C. Shieh, M. Coghlan, J. P. Sullivan, and M. Gopalakrishnan Potassium Channels: Molecular Defects, Diseases, and Therapeutic Opportunities Pharmacol. Rev., December 1, 2000; 52(4): 557 - 594. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M Nerbonne Molecular basis of functional voltage-gated K+ channel diversity in the mammalian myocardium J. Physiol., June 1, 2000; 525(2): 285 - 298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nattel, D. M. Roden, and D. Escande A spotlight on electrophysiological remodeling and the molecular biology of ion channels Cardiovasc Res, May 1, 1999; 42(2): 267 - 269. [Full Text] [PDF]
|
|