AJP - Heart and Circulatory Physiology, Vol 269, Issue 2 463-H472, Copyright © 1995 by American Physiological Society

ARTICLES

Comparative mechanisms of 4-aminopyridine-resistant Ito in human and rabbit atrial myocytes

G. R. Li, J. Feng, Z. Wang, B. Fermini and S. Nattel
Department of Medicine, Montreal Heart Institute, University of Montreal, Quebec, Canada.

The cardiac transient outward current (Ito) has been shown in several species to consist of two components: 1) a 4-aminopyridine (4-AP)-sensitive component (Ito1) and 2) a 4-AP-resistant component (Ito2). In rabbits, Ito2 is a Ca(2+)-dependent Cl- current [ICl(Ca)]; similar mechanisms have been suggested to underlie Ito2 in human atrium. We used whole cell patch-clamp techniques to define the mechanism of Ito2 (defined as the component resistant to 5 mM 4-AP) in human atrial myocytes, with parallel experiments performed in rabbit atrial cells. In rabbit atrium, Ito2 activated more slowly than Ito1 and had a bell-shaped current-voltage of Ito with properties similar to Ito2 in the rabbit, and a similar component recorded with pipette K+ replaced by Cs+ was suppressed by the substitution of methanesulfonate for Cl- in the superfusate. In human cells, a 4-AP-resistant Ito2 was recorded at a depolarizing pulse frequency of 1 Hz, but not at 0.1 Hz. Ito2 activated rapidly and inactivated earlier than Ito1, whereas its I-V relation was linear like that of Ito1. Ryanodine had no effect on human atrial Ito. When K(+)-free pipette solutions were used, no Ito was recorded in 30 human atrial myocytes, and external Cl- replacement with methanesulfonate failed to reveal an Ito. In 13 human myocytes, isoproterenol increased ICa but failed to activate an Ito compatible with ICl(Ca). Whereas caffeine suppressed human atrial Ito, it also suppressed Ito1 [in the presence of 200 microM Cd2+ to block ICa and 5 mM intracellular ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid to buffer intracellular Ca2+] in both human and rabbit atrium, indicating an action unrelated to Ca(2+)-triggered Ca2+ release. In conclusion, we were unable to demonstrate the presence of ICl(Ca) in human atrial myocytes, and the 4-AP-resistant component of Ito appeared to be due to 4-AP unblocking.

This article has been cited by other articles:

				H. E. D. J. ter Keurs and P. A. Boyden Calcium and Arrhythmogenesis Physiol Rev, April 1, 2007; 87(2): 457 - 506. [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]

				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.-R. Li and C. M. Baumgarten Modulation of cardiac Na+ current by gadolinium, a blocker of stretch-induced arrhythmias Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H272 - H279. [Abstract] [Full Text] [PDF]

				A. O. Verkerk, M. W. Veldkamp, L. N. Bouman, and A. C. G. van Ginneken Calcium-Activated Cl- Current Contributes to Delayed Afterdepolarizations in Single Purkinje and Ventricular Myocytes Circulation, June 6, 2000; 101(22): 2639 - 2644. [Abstract] [Full Text] [PDF]

				J. R. Hume, D. Duan, M. L. Collier, J. Yamazaki, and B. Horowitz Anion Transport in Heart Physiol Rev, January 1, 2000; 80(1): 31 - 81. [Abstract] [Full Text] [PDF]

				E. Carmeliet Cardiac Ionic Currents and Acute Ischemia: From Channels to Arrhythmias Physiol Rev, July 1, 1999; 79(3): 917 - 1017. [Abstract] [Full Text] [PDF]

				H.-S. Wang, J. E. Dixon, and D. McKinnon Unexpected and Differential Effects of Cl- Channel Blockers on the Kv4.3 and Kv4.2 K+ Channels : Implications for the Study of the Ito2 Current Circ. Res., November 19, 1997; 81(5): 711 - 718. [Abstract] [Full Text]

				G.-R. Li, M. Zhang, L. S. Satin, and C. M. Baumgarten Biphasic effects of cell volume on excitation-contraction coupling in rabbit ventricular myocytes Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1270 - H1277. [Abstract] [Full Text] [PDF]