© 2004 by European Society of Cardiology
Copyright © 2004, European Society of Cardiology
Pharmacology of cardiac potassium channels
Department of Pharmacology, School of Medicine, Universidad Complutense, 28040 Madrid, Spain
* Corresponding author. Tel.: +34-91-3941472; fax: +34-91-3941470. Email address: jtamargo{at}med.ucm.es
Cardiac K+ channels are membrane-spanning proteins that allow the passive movement of K+ ions across the cell membrane along its electrochemical gradient. They regulate the resting membrane potential, the frequency of pacemaker cells and the shape and duration of the cardiac action potential. Additionally, they have been recognized as potential targets for the actions of neurotransmitters and hormones and class III antiarrhythmic drugs that prolong the action potential duration (APD) and refractoriness and have been found effective to prevent/suppress cardiac arrhythmias. In the human heart, K+ channels include voltage-gated channels, such as the rapidly activating and inactivating transient outward current (Ito1), the ultrarapid (IKur), rapid (IKr) and slow (IKs) components of the delayed rectifier current and the inward rectifier current (IK1), the ligand-gated channels, including the adenosine triphosphate-sensitive (IKATP) and the acetylcholine-activated (IKAch) currents and the leak channels. Changes in the expression of K+ channels explain the regional variations in the morphology and duration of the cardiac action potential among different cardiac regions and are influenced by heart rate, intracellular signalling pathways, drugs and cardiovascular disorders. A progressive number of cardiac and noncardiac drugs block cardiac K+ channels and can cause a marked prolongation of the action potential duration (i.e. an acquired long QT syndrome, LQTS) and a distinct polymorphic ventricular tachycardia termed torsades de pointes. In addition, mutations in the genes encoding IKr (KCNH2/KCNE2) and IKs (KCNQ1/KCNE1) channels have been identified in some types of the congenital long QT syndrome. This review concentrates on the function, molecular determinants, regulation and, particularly, on the mechanism of action of drugs modulating the K+ channels present in the sarcolemma of human cardiac myocytes that contribute to the different phases of the cardiac action potential under physiological and pathological conditions.
KEYWORDS K+ channels; Cardiomyocytes; Pharmacology; Cardiac arrhythmias; Antiarrhythmic agents; Torsades de pointes
Time for primary review 26 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. L. Stables and M. J. Curtis Development and characterization of a mouse in vitro model of ischaemia-induced ventricular fibrillation Cardiovasc Res, July 15, 2009; 83(2): 397 - 404. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Gomez, L. Nunez, M. Vaquero, I. Amoros, A. Barana, T. de Prada, C. Macaya, L. Maroto, E. Rodriguez, R. Caballero, et al. Nitric oxide inhibits Kv4.3 and human cardiac transient outward potassium current (Ito1) Cardiovasc Res, December 1, 2008; 80(3): 375 - 384. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Sanchez-Quinones, F. Marin, V. Roldan, and G.Y.H. Lip The impact of statin use on atrial fibrillation QJM, November 1, 2008; 101(11): 845 - 861. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Delpon, J. M. Cordeiro, L. Nunez, P. E. B. Thomsen, A. Guerchicoff, G. D. Pollevick, Y. Wu, J. K. Kanters, C. T. Larsen, E. Burashnikov, et al. Functional Effects of KCNE3 Mutation and Its Role in the Development of Brugada Syndrome Circ Arrhythm Electrophysiol, August 1, 2008; 1(3): 209 - 218. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Mangoni and J. Nargeot Genesis and Regulation of the Heart Automaticity Physiol Rev, July 1, 2008; 88(3): 919 - 982. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Heitzmann and R. Warth Physiology and Pathophysiology of Potassium Channels in Gastrointestinal Epithelia Physiol Rev, July 1, 2008; 88(3): 1119 - 1182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. C. L. Bett and R. L. Rasmusson Modification of K+ channel-drug interactions by ancillary subunits J. Physiol., February 15, 2008; 586(4): 929 - 950. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Ko, E. D. Burg, O. Platoshyn, J. Msefya, A. L. Firth, and J. X.-J. Yuan Functional characterization of voltage-gated K+ channels in mouse pulmonary artery smooth muscle cells Am J Physiol Cell Physiol, September 1, 2007; 293(3): C928 - C937. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Chen, R. M. Wilson, H. Kubo, R. M. Berretta, D. M. Harris, X. Zhang, N. Jaleel, S. M. MacDonnell, C. Bearzi, J. Tillmanns, et al. Adolescent Feline Heart Contains a Population of Small, Proliferative Ventricular Myocytes With Immature Physiological Properties Circ. Res., March 2, 2007; 100(4): 536 - 544. [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]
|
|
|
|
|
|
Z. Mustapha, L. Pang, and S. Nattel Characterization of the cardiac KCNE1 gene promoter Cardiovasc Res, January 1, 2007; 73(1): 82 - 91. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Tutor, E. Delpon, R. Caballero, R. Gomez, L. Nunez, M. Vaquero, J. Tamargo, F. Mayor Jr., and P. Penela Association of 14-3-3 Proteins to beta1-Adrenergic Receptors Modulates Kv11.1 K+ Channel Activity in Recombinant Systems Mol. Biol. Cell, November 1, 2006; 17(11): 4666 - 4674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Nunez, M. Vaquero, R. Gomez, R. Caballero, P. Mateos-Caceres, C. Macaya, I. Iriepa, E. Galvez, A. Lopez-Farre, J. Tamargo, et al. Nitric oxide blocks hKv1.5 channels by S-nitrosylation and by a cyclic GMP-dependent mechanism Cardiovasc Res, October 1, 2006; 72(1): 80 - 89. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Writing Committee Members, V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: full text: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society Europace, September 1, 2006; 8(9): 651 - 745. [Full Text] [PDF]
|
|
|
|
 |
|
 V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society J. Am. Coll. Cardiol., August 15, 2006; 48(4): e149 - e246. [Full Text] [PDF]
|
|
|
|
 |
|
 V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society Circulation, August 15, 2006; 114(7): e257 - e354. [Full Text] [PDF]
|
|
|
|
|
|
A. Varro and J. Gy. Papp Low penetrance, subclinical congenital LQTS: Concealed LQTS or silent LQTS? Cardiovasc Res, June 1, 2006; 70(3): 404 - 406. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Rossokhin, G. Teodorescu, S. Grissmer, and B. S. Zhorov Interaction of d-Tubocurarine with Potassium Channels: Molecular Modeling and Ligand Binding Mol. Pharmacol., April 1, 2006; 69(4): 1356 - 1365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.-J. Chang, M.-J. Su, S.-C. Kuo, T.-P. Lin, and Y.-S. Lee Multiple Cellular Electrophysiological Effects of a Novel Antiarrhythmic Furoquinoline Derivative HA-7 [N-Benzyl-7-methoxy-2,3,4,9-tetrahydrofuro[2,3-b]quinoline-3,4-dione] in Guinea Pig Cardiac Preparations J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 380 - 391. [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]
|
|
|
|
 |
|
 N. W. G. Lambrecht, I. Yakubov, D. Scott, and G. Sachs Identification of the K efflux channel coupled to the gastric H-K-ATPase during acid secretion Physiol Genomics, March 21, 2005; 21(1): 81 - 91. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Garcia-Dorado, K.-D. Schluter, E. A. Martinson, and H. M. Piper Which papers are most interesting to the readers of Cardiovascular Research? Information from download monitoring Cardiovasc Res, January 1, 2005; 65(1): 1 - 5. [Full Text] [PDF]
|
|
|
|
 |
|
 B. P. Ander, A. R. Weber, P. P. Rampersad, J. S. C. Gilchrist, G. N. Pierce, and A. Lukas Dietary Flaxseed Protects against Ventricular Fibrillation Induced by Ischemia-Reperfusion in Normal and Hypercholesterolemic Rabbits J. Nutr., December 1, 2004; 134(12): 3250 - 3256. [Abstract] [Full Text] [PDF]
|
|