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First published online on June 11, 2004.
Copyright © 2004 by The Physiological Society
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jphysiol.2004.063347v1
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Received March 3, 2004
Revised April 8, 2004
Accepted after revision June 10, 2004

HETEROGENEOUS EXPRESSION OF REPOLARIZING, VOLTAGE-GATED K+ CURRENTS IN ADULT MOUSE VENTRICLES

Sylvain Brunet1, Franck Aimond1, Weinong Guo1, Huilin Li1, Jodene Eldstrom2, David Fedida2, Kathryn A. Yamada3, and Jeanne M. Nerbonne3*

1 Washington University Medical School
2 University of British Columbia
3 Washington University School of Medicine

* To whom correspondence should be addressed. E-mail: jnerbonne{at}msnotes.wustl.edu.

Previous studies have documented the expression of four kinetically-distinct voltage-gated K+(Kv) currents, Ito,f, Ito,s, IK,slow and Iss, in mouse ventricular myocytes and demonstrated that Ito,f and Ito,s are differentially expressed in the left ventricular apex and the interventricular septum. The experiments here were undertaken to test the hypothesis that there are further regional differences in the expression of Kv currents or the Kv subunits (Kv4.2, Kv4.3, KChIP2, Kv1.5, Kv2.1) encoding these currents in adult male and female (C57BL6) mouse ventricles. Whole-cell voltage-clamp recordings revealed that mean (± SEM) peak outward K+ current and Ito,f densities are significantly (P < .001) higher in cells isolated from the right (RV), than the left (LV), ventricles. Within the LV, peak outward K+ current and Ito,f densities are significantly (P < .05) higher in cells from the apex than the base. In addition, Ito,f and IK,slow densities are lower in cells isolated from the endocardial (ENDO), than the epicardial (EPI), surface of the LV wall. Importantly, similar to LV apex cells, Ito,s is not detected in RV, LV base, LV EPI or LV ENDO myocytes. No measurable differences in K+ current densities or properties are evident in RV or LV cells from adult male and female mice, although Ito,f, Ito,s, IK,slow and Iss densities are significantly (P < .01) higher, and APD50 are significantly (P < .05) shorter in male septum cells. Western blot analysis revealed that the expression levels of Kv4.2, Kv4.3, KChIP2, Kv1.5 and Kv2.1 are similar in male and female ventricles. In addition, consistent with the similarities in repolarizing Kv current densities, no measurable differences in ECG parameters, including QTc intervals, are detected in telemetric recordings from adult male and female (C57BL6) mice.


Key words: Cardiac myocytes • K+-channel expression • Potassium current







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