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First published online on July 22, 2004.
 Copyright © 2004 by The Physiological Society
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Received May 10, 2004
Revised June 4, 2004
Accepted after revision July 19, 2004

Functional Properties of K+ Currents in Adult Mouse Ventricular Myocytes

Judith Brouillette1, Robert B Clark2, Wayne R Giles3, and Céline Fiset4*

1 Montreal Heart Institute and University of Montreal
2 University of Calgary
3 University of California
4 Montreal Heart Institute

* To whom correspondence should be addressed. E-mail: fiset{at}icm.umontreal.ca.

Although the K+ currents expressed in ventricles of adult mice have been studied extensively, detailed information concerning their relative sizes and biophysical properties in ventricle and atrium is lacking. Here we describe and validate pharmacological and biophysical methods that can be used to isolate the three main time- and voltage-dependent outward K+ currents which modulate action potential repolarization. A Ca2+-independent transient outward K+ current, Ito, can be separated from total outward current using an "inactivating prepulse". The rapidly activating, slowly inactivating delayed rectifier K+ current, IKur, can be isolated using sub-millimolar concentrations of 4-aminopyridine (4-AP). The remaining K+ current, Iss, can be obtained by combining these two procedures: (i) inactivating Ito and (ii) eliminating IKur by application of low concentration of 4-AP. Iss activates relatively slowly and shows very little inactivation, even during depolarizations lasting several seconds. Our findings also show that the rate of reactivation of Ito is more than 20-fold faster than that of IKur. These results demonstrate that the outward K+ currents in mouse ventricles can be separated based on their distinct time- and voltage-dependence, and different sensitivities to 4-AP. Data obtained at both 22oC and 32oC demonstrate that although the duration of the inactivating prepulse has to be adapted for the recording temperature, this approach for separation of K+ current components is also valid at more physiological temperatures. To demonstrate that these methods also allow separation of these K+ currents in other cell types, we have applied this same approach to myocytes from mouse atria. Molecular approaches were also used to compare the expression levels of different K+ channels in mouse atrium and ventricle. In conclusion, these findings provide new insights into the functional roles of IKur, Ito, and Iss during action potential repolarization.


Key words: Electrophysiology • Heart • K+-currents




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