© 1999 American Heart Association, Inc.
Original Contribution |
Potential Molecular Basis of Different Physiological Properties of the Transient Outward K+ Current in Rabbit and Human Atrial Myocytes
From the Department of Medicine (Z.W., J.F., H.S., S.N.), Montreal Heart Institute, Department of Medicine, University of Montreal (Z.W., S.N.), and the Department of Pharmacology and Therapeutics (S.N.), McGill University, Montreal, Quebec, Canada, and the Department of Cell Biology (A.P., J.M.N.), Washington University, St. Louis, Mo.
Correspondence to Zhiguo Wang, PhD, Research Center, Montreal Heart Institute, 5000 Belanger East, Montreal, Quebec, Canada H1T 1C8.
Abstract—The properties of the transient outward current (Ito) differ between rabbit and human atrial myocytes. In particular, rabbit Ito is known to recover more slowly than its human counterpart and to show much more frequency dependence. To assess the possibility that these physiological differences may reflect differing expression of K+ channel subunit gene products, we used a combination of whole-cell voltage-clamp, heterologous expression, pharmacological, antisense, and Western blot techniques. The inactivation of Ito in rabbit atrial myocytes was significantly slowed by hydrogen peroxide, with human Ito being unaffected. Use-dependent unblocking with 4-aminopyridine was not seen for rabbit Ito nor for Kv1.4 currents in Xenopusoocytes, whereas human Ito showed strong use-dependent unblock (as did Kv4 currents). Western blots indicated the presence of Kv4 proteins in both human and rabbit atrial membranes, but Kv1.4 was only detected in the rabbit. Antisense oligodeoxynucleotides directed against Kv4.3, Kv4.2, or Kv1.4 subunit sequences significantly inhibited Ito current density in cultured rabbit atrial myocytes, whereas only Kv4.3 antisense significantly inhibited Ito in human cells. Neither mismatch oligodeoxynucleotides nor vehicle altered currents in either species. We conclude that, unlike human atrial myocytes, rabbit atrial myocytes express Kv1.4 channel subunits, which likely contribute to a number of important physiological differences in Ito properties between the species. To our knowledge, these studies constitute the first demonstration of a functional role for Kv1.4 channels in cardiac membranes and provide insights into the molecular mechanisms of an important cardiac repolarizing current.
Key Words: electrophysiology • cardiac arrhythmia • action potential • antiarrhythmic drug
This article has been cited by other articles:
 |
|
 |
|
  M. M. Maleckar, J. L. Greenstein, W. R. Giles, and N. A. Trayanova K+ current changes account for the rate dependence of the action potential in the human atrial myocyte Am J Physiol Heart Circ Physiol, October 1, 2009; 297(4): H1398 - H1410. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Laszlo, C. Eick, N. Rueb, S. Weretka, H.-J. Weig, J. Schreieck, and R. F Bosch Inhibition of the renin-angiotensin system: effects on tachycardia-induced early electrical remodelling in rabbit atrium Journal of Renin-Angiotensin-Aldosterone System, September 1, 2008; 9(3): 125 - 132. [Abstract] [PDF]
|
|
|
|
|
|
V. E. Bondarenko and R. L. Rasmusson Simulations of propagated mouse ventricular action potentials: effects of molecular heterogeneity Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1816 - H1832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Xiao, X. Luo, H. Lin, Y. Zhang, Y. Lu, N. Wang, Y. Zhang, B. Yang, and Z. Wang MicroRNA miR-133 Represses HERG K+ Channel Expression Contributing to QT Prolongation in Diabetic Hearts J. Biol. Chem., April 27, 2007; 282(17): 12363 - 12367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. O. Tellez, H. Dobrzynski, I. D. Greener, G. M. Graham, E. Laing, H. Honjo, S. J. Hubbard, M. R. Boyett, and R. Billeter Differential Expression of Ion Channel Transcripts in Atrial Muscle and Sinoatrial Node in Rabbit Circ. Res., December 8, 2006; 99(12): 1384 - 1393. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Ehrlich, C. Hoche, P. Coutu, C. Metz-Weidmann, W. Dittrich, S. H. Hohnloser, S. Nattel, and H. Gogelein Properties of a Time-Dependent Potassium Current in Pig Atrium: Evidence for a Role of Kv1.5 in Repolarization J. Pharmacol. Exp. Ther., November 1, 2006; 319(2): 898 - 906. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Dong, X. Sun, A. A. Prinz, and H.-S. Wang Effect of simulated Ito on guinea pig and canine ventricular action potential morphology Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H631 - H637. [Abstract] [Full Text] [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]
|
|
|
|
 |
|
 Y. Wang, J. Cheng, R. W. Joyner, M. B. Wagner, and J. A. Hill Remodeling of Early-Phase Repolarization: A Mechanism of Abnormal Impulse Conduction in Heart Failure Circulation, April 18, 2006; 113(15): 1849 - 1856. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.-L. Wang, G.-X. Wang, S. Yamamoto, L. Ye, H. Baxter, J. R Hume, and D. Duan Molecular mechanisms of regulation of fast-inactivating voltage-dependent transient outward K+ current in mouse heart by cell volume changes J. Physiol., October 15, 2005; 568(2): 423 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Nerbonne and R. S. Kass Molecular Physiology of Cardiac Repolarization Physiol Rev, October 1, 2005; 85(4): 1205 - 1253. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Ren and C. M. Baumgarten Antagonistic regulation of swelling-activated Cl- current in rabbit ventricle by Src and EGFR protein tyrosine kinases Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2628 - H2636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. G. Akar, R. C. Wu, G. J. Juang, Y. Tian, M. Burysek, D. DiSilvestre, W. Xiong, A. A. Armoundas, and G. F. Tomaselli Molecular mechanisms underlying K+ current downregulation in canine tachycardia-induced heart failure Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2887 - H2896. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Rose, A. A. Armoundas, Y. Tian, D. DiSilvestre, M. Burysek, V. Halperin, B. O'Rourke, D. A. Kass, E. Marban, and G. F. Tomaselli Molecular correlates of altered expression of potassium currents in failing rabbit myocardium Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2077 - H2087. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Jang, L. E.-C. Leong, L. T. Hoang, P. H. Wang, G. A. Gutman, and B. L. Semler Structurally Distinct Elements Mediate Internal Ribosome Entry within the 5'-Noncoding Region of a Voltage-gated Potassium Channel mRNA J. Biol. Chem., November 12, 2004; 279(46): 47419 - 47430. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Zhabyeyev, T. Asai, S. Missan, and T. F. McDonald Transient outward current carried by inwardly rectifying K+ channels in guinea pig ventricular myocytes dialyzed with low-K+ solution Am J Physiol Cell Physiol, November 1, 2004; 287(5): C1396 - C1403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Bassani, J. Altamirano, J. L. Puglisi, and D. M. Bers Action potential duration determines sarcoplasmic reticulum Ca2+ reloading in mammalian ventricular myocytes J. Physiol., September 1, 2004; 559(2): 593 - 609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Birnbaum, A. W. Varga, L.-L. Yuan, A. E. Anderson, J. D. Sweatt, and L. A. Schrader Structure and Function of Kv4-Family Transient Potassium Channels Physiol Rev, July 1, 2004; 84(3): 803 - 833. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. G. Akar, R. C. Wu, I. Deschenes, A. A. Armoundas, V. Piacentino III, S. R. Houser, and G. F. Tomaselli Phenotypic differences in transient outward K+ current of human and canine ventricular myocytes: insights into molecular composition of ventricular Ito Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H602 - H609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Li, W. Guo, K. A. Yamada, and J. M. Nerbonne Selective elimination of IK,slow1 in mouse ventricular myocytes expressing a dominant negative Kv1.5{alpha} subunit Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H319 - H328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zicha, I. Moss, B. Allen, A. Varro, J. Papp, R. Dumaine, C. Antzelevich, and S. Nattel Molecular basis of species-specific expression of repolarizing K+ currents in the heart Am J Physiol Heart Circ Physiol, October 1, 2003; 285(4): H1641 - H1649. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. F. Bosch, C. R. Scherer, N. Rub, S. Wohrl, K. Steinmeyer, H. Haase, A. E. Busch, L. Seipel, and V. Kuhlkamp Molecular mechanisms of early electrical remodeling: transcriptional downregulation of ion channel subunits reduces ICa,L and Ito in rapid atrial pacing in rabbits J. Am. Coll. Cardiol., March 5, 2003; 41(5): 858 - 869. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. lost, L. Virag, A. Varro, and J. Gy. Papp Comparison of the Effect of Class IA Antiarrhythmic Drugs on Transmembrane Potassium Currents in Rabbit Ventricular Myocytes Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2003; 8(1): 31 - 41. [Abstract] [PDF]
|
|
|
|
|
|
I. Moreno, R. Caballero, T. Gonzalez, C. Arias, C. Valenzuela, I. Iriepa, E. Galvez, J. Tamargo, and E. Delpon Effects of Irbesartan on Cloned Potassium Channels Involved in Human Cardiac Repolarization J. Pharmacol. Exp. Ther., February 1, 2003; 304(2): 862 - 873. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Dong, Y. Duan, J. Guo, D. E Roach, S. L Swirp, L. Wang, J.P Lees-Miller, R.S Sheldon, J. D Molkentin, and H. J Duff Overexpression of calcineurin in mouse causes sudden cardiac death associated with decreased density of K+ channels Cardiovasc Res, February 1, 2003; 57(2): 320 - 332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wang, M. J Morales, Y.-J. Qu, G. C L Bett, H. C Strauss, and R. L Rasmusson Kv1.4 channel block by quinidine: evidence for a drug-induced allosteric effect J. Physiol., January 15, 2003; 546(2): 387 - 401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Han, L. Zhang, G. Schram, and S. Nattel Properties of potassium currents in Purkinje cells of failing human hearts Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2495 - H2503. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Han, W. Bao, Z. Wang, and S. Nattel Comparison of Ion-Channel Subunit Expression in Canine Cardiac Purkinje Fibers and Ventricular Muscle Circ. Res., November 1, 2002; 91(9): 790 - 797. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kaprielian, R. Sah, T. Nguyen, A. D. Wickenden, and P. H. Backx Myocardial infarction in rat eliminates regional heterogeneity of AP profiles, Ito K+ currents, and [Ca2+]i transients Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H1157 - H1168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Padanilam, T. Lu, T. Hoshi, B. A. Padanilam, E. F. Shibata, and H.-C. Lee Molecular Determinants of Intracellular pH Modulation of Human Kv1.4 N-Type Inactivation Mol. Pharmacol., July 1, 2002; 62(1): 127 - 134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xu, P. H. Dong, Z. Zhang, G. U. Ahmmed, and N. Chiamvimonvat Presence of a calcium-activated chloride current in mouse ventricular myocytes Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H302 - H314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Schram, M. Pourrier, P. Melnyk, and S. Nattel Differential Distribution of Cardiac Ion Channel Expression as a Basis for Regional Specialization in Electrical Function Circ. Res., May 17, 2002; 90(9): 939 - 950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. F Bosch and S. Nattel Cellular electrophysiology of atrial fibrillation Cardiovasc Res, May 1, 2002; 54(2): 259 - 269. [Full Text] [PDF]
|
|
|
|
|
|
Z. Kassiri, C. Zobel, T.-T. T. Nguyen, J. D. Molkentin, and P. H. Backx Reduction of Ito Causes Hypertrophy in Neonatal Rat Ventricular Myocytes Circ. Res., March 22, 2002; 90(5): 578 - 585. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Guo, H. Li, F. Aimond, D. C. Johns, K. J. Rhodes, J. S. Trimmer, and J. M. Nerbonne Role of Heteromultimers in the Generation of Myocardial Transient Outward K+ Currents Circ. Res., March 22, 2002; 90(5): 586 - 593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Nerbonne, C. G. Nichols, T. L. Schwarz, and D. Escande Genetic Manipulation of Cardiac K+ Channel Function in Mice: What Have We Learned, and Where Do We Go From Here? Circ. Res., November 23, 2001; 89(11): 944 - 956. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Li, W. Guo, H. Xu, R. Hood, A. T. Benedict, and J. M. Nerbonne Functional expression of a GFP-tagged Kv1.5 alpha -subunit in mouse ventricle Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H1955 - H1967. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Decher, O. Uyguner, C. R Scherer, B. Karaman, M. Yuksel-Apak, A. E Busch, K. Steinmeyer, and B. Wollnik hKChIP2 is a functional modifier of hKv4.3 potassium channels: Cloning and expression of a short hKChIP2 splice variant Cardiovasc Res, November 1, 2001; 52(2): 255 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wang, H. Han, L. Zhang, H. Shi, G. Schram, S. Nattel, and Z. Wang Expression of Multiple Subtypes of Muscarinic Receptors and Cellular Distribution in the Human Heart Mol. Pharmacol., April 16, 2001; 59(5): 1029 - 1036. [Abstract] [Full Text]
|
|
|
|
|
|
T. González, M. Longobardo, R. Caballero, E. Delpón, J. Tamargo, and C. Valenzuela Effects of Bupivacaine and a Novel Local Anesthetic, IQB-9302, on Human Cardiac K+ Channels J. Pharmacol. Exp. Ther., April 13, 2001; 296(2): 573 - 583. [Abstract] [Full Text]
|
|
|
|
|
|
R. Caballero, E. Delpón, C. Valenzuela, M. Longobardo, T. González, and J. Tamargo Direct Effects of Candesartan and Eprosartan on Human Cloned Potassium Channels Involved in Cardiac Repolarization Mol. Pharmacol., April 1, 2001; 59(4): 825 - 836. [Abstract] [Full Text]
|
|
|
|
|
|
M. A. Allessie, P. A. Boyden, A. J. Camm, A. G. Kleber, M. J. Lab, M. J. Legato, M. R. Rosen, P. J. Schwartz, P. M. Spooner, D. R. Van Wagoner, et al. Pathophysiology and Prevention of Atrial Fibrillation Circulation, February 6, 2001; 103(5): 769 - 777. [Full Text] [PDF]
|
|
|
|
|
|
L. Yue, Z. Wang, H. Rindt, and S. Nattel Molecular evidence for a role of Shaw (Kv3) potassium channel subunits in potassium currents of dog atrium J. Physiol., September 15, 2000; 527(3): 467 - 478. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wang, H. Shi, L. Zhang, M. Pourrier, B. Yang, S. Nattel, and Z. Wang Nicotine Is a Potent Blocker of the Cardiac A-Type K+ Channels : Effects on Cloned Kv4.3 Channels and Native Transient Outward Current Circulation, September 5, 2000; 102(10): 1165 - 1171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Vincent, N. J. Lautermilch, and N. C. Spitzer Antisense Suppression of Potassium Channel Expression Demonstrates Its Role in Maturation of the Action Potential J. Neurosci., August 15, 2000; 20(16): 6087 - 6094. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T W Claydon, M R Boyett, A Sivaprasadarao, K Ishii, J M Owen, H A O'Beirne, R Leach, K Komukai, and C H Orchard Inhibition of the K+ channel Kv1.4 by acidosis: protonation of an extracellular histidine slows the recovery from N-type inactivation J. Physiol., July 15, 2000; 526(2): 253 - 264. [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]
|
|
|
|
|
|
W. Guo, H. Xu, B. London, and J. M Nerbonne Molecular basis of transient outward K+ current diversity in mouse ventricular myocytes J. Physiol., December 15, 1999; 521(3): 587 - 599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Xu, D. M. Barry, H. Li, S. Brunet, W. Guo, and J. M. Nerbonne Attenuation of the Slow Component of Delayed Rectification, Action Potential Prolongation, and Triggered Activity in Mice Expressing a Dominant-Negative Kv2 {alpha} Subunit Circ. Res., October 1, 1999; 85(7): 623 - 633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kiyosue and M. Arita Altered expression of cardiac K+ channel genes during sub-acute and healing phases of myocardial infarction Cardiovasc Res, October 1, 1999; 44(1): 13 - 16. [Full Text] [PDF]
|
|
|
|
|
|
D. McKinnon Molecular Identity of Ito : Kv1.4 Redux Circ. Res., March 19, 1999; 84(5): 620 - 622. [Full Text] [PDF]
|
|
|
|
|
|
M. Song, G. Helguera, M. Eghbali, N. Zhu, M. M. Zarei, R. Olcese, L. Toro, and E. Stefani Remodeling of Kv4.3 Potassium Channel Gene Expression under the Control of Sex Hormones J. Biol. Chem., August 17, 2001; 276(34): 31883 - 31890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wang, B. Yang, Y. Zhang, H. Han, J. Wang, H. Shi, and Z. Wang Different Subtypes of alpha 1-Adrenoceptor Modulate Different K+ Currents via Different Signaling Pathways in Canine Ventricular Myocytes J. Biol. Chem., October 26, 2001; 276(44): 40811 - 40816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Kassiri, C. Zobel, T.-T. T. Nguyen, J. D. Molkentin, and P. H. Backx Reduction of Ito Causes Hypertrophy in Neonatal Rat Ventricular Myocytes Circ. Res., March 22, 2002; 90(5): 578 - 585. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Guo, H. Li, F. Aimond, D. C. Johns, K. J. Rhodes, J. S. Trimmer, and J. M. Nerbonne Role of Heteromultimers in the Generation of Myocardial Transient Outward K+ Currents Circ. Res., March 22, 2002; 90(5): 586 - 593. [Abstract] [Full Text] [PDF]
|
|