HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 286/6/H2342    most recent 00793.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Hua, F. Articles by Gilmour, R. F. Search for Related Content PubMed PubMed Citation Articles by Hua, F. Articles by Gilmour, R. F., Jr.

Suppression of electrical alternans by overexpression of HERG in canine ventricular myocytes

¹Department of Biomedical Sciences, Cornell University, Ithaca, New York 14853; and ²Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, Maryland 21205

Submitted 15 August 2003 ; accepted in final form 6 February 2004

Suppression of electrical alternans may be antiarrhythmic. Our previous computer simulations have suggested that increasing the rapid component of the delayed rectifier K⁺ current (I_Kr) suppresses alternans. To test this hypothesis, I_Kr in isolated canine ventricular myocytes was increased by infection with an adenovirus containing the gene for the pore-forming domain of I_Kr [human ether-a-go-go gene (HERG)]. With the use of the perforated or whole cell patch-clamp technique, action potentials recorded at different pacing cycle lengths (CLs) were applied to the myocytes as the command waveforms. HERG infection markedly increased peak I_Kr during the action potential (from 0.54 ± 0.03 pA/pF in control to 3.60 ± 0.81 pA/pF). Rate-dependent alterations of peak I_Kr were similar for freshly isolated myocytes and HERG-infected myocytes. In both cell types, I_Kr increased when CL decreased from 1,000 to 500 ms and then decreased progressively as CL decreased further. During alternans at CL = 170 ms, peak I_Kr was larger for the short than for the long action potential for both groups, but the difference in peak I_Kr was larger for HERG-infected myocytes. The voltage at which peak I_Kr occurred was significantly less negative in HERG-infected myocytes, in association with shifts of the steady-state voltage-dependent activation and inactivation curves to less negative potentials. Pacing at short CL induced stable alternans in freshly isolated myocytes and in cultured myocytes without HERG infection, but not in HERG-infected myocytes. These data support the idea that increasing I_Kr may be a viable approach to suppressing electrical alternans.

delayed rectifier; ventricular arrhythmias

This article has been cited by other articles:

				A. Sridhar, Y. Nishijima, D. Terentyev, R. Terentyeva, R. Uelmen, M. Kukielka, I. M. Bonilla, G. A. Robertson, S. Gyorke, G. E. Billman, et al. Repolarization abnormalities and afterdepolarizations in a canine model of sudden cardiac death Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2008; 295(5): R1463 - R1472. [Abstract] [Full Text] [PDF]

				J. M. Cordeiro, J. E. Malone, J. M. Di Diego, F. S. Scornik, G. L. Aistrup, C. Antzelevitch, and J. A. Wasserstrom Cellular and subcellular alternans in the canine left ventricle Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3506 - H3516. [Abstract] [Full Text] [PDF]

				L. M. Livshitz and Y. Rudy Regulation of Ca2+ and electrical alternans in cardiac myocytes: role of CAMKII and repolarizing currents Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2854 - H2866. [Abstract] [Full Text] [PDF]