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Cardiovasc Res. 2003 Apr 1;58(1):89-98.

Calcium-activated transient outward chloride current and phase 1 repolarization of swine ventricular action potential.

Author information

  • 1Institute of Cardiovascular Science and Medicine/Department of Medicine, The University of Hong Kong, Hong Kong SAR, China. grli@hkucc.hku.hk

Abstract

OBJECTIVE:

It is unknown whether 4-aminopyridine- (4-AP-) sensitive transient outward K(+) current (I(to1)) and/or Ca(2+)-activated transient outward Cl(-) current (I(Ca.Cl) or I(to2)) contribute(s) to phase 1 repolarization of pig ventricular action potential (AP). The purpose of the present study was to determine ionic contribution of the phase 1 repolarization of AP in pig ventricle.

METHODS:

We used whole-cell patch techniques to record APs and membrane currents, and Western immunoblotting analysis to detect expression of I(to1) protein (Kv4.2 or Kv4.3) in pig ventricular myocytes.

RESULTS:

A transient outward current (I(to)) was activated upon depolarization voltage steps to between -10 and +60 mV from -50 mV in pig ventricular cells, and the I(to) was resistant to 4-AP application, but sensitive to the inhibition by ryanodine (10 micromol/l) and the Ca(2+) channel blockade, and the Cl(-) channel blocker 4,4'-diisothiocyanostilben-2,2'disulfonic acid (DIDS, 150 micromol/l). The current was diminished by external Cl(-) (Cl(-)(o)) replacement and showed a 'bell-shaped' I-V relationship at room temperature, typical of I(to2). No difference in I(to2) was observed in the regional cells from epicardium, midmyocardium, and endocardium of left ventricle. APs showed significant phase 1 and 'spike and dome' in pig ventricular myocytes. The phase 1 and 'spike and dome' of APs were not affected by 4-AP (3 mmol/l), but abolished by replacing Cl(-)(o) and by application of 100 micromol/l DIDS, suggesting I(to2) contribution. Western immunoblotting analysis showed no evidence for the expression of 4-AP-sensitive I(to1) channel protein (Kv4.2 or Kv4.3) in pig ventricular cells.

CONCLUSION:

The results indicate that 4-AP-sensitive I(to1) is not expressed, and only Ca(2+)-activated I(to2) is present in pig cardiac cells, which contributes importantly to the phase 1 repolarization of ventricular APs in this species.

PMID:
12667949
[PubMed - indexed for MEDLINE]
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