| 12667949 |
Li GR, Du XL, Siow YL, O K, Tse HF, Lau CP: Calcium-activated transient outward chloride current and phase 1 repolarization of swine ventricular action potential. Cardiovasc Res. 2003 Apr 1;58(1):89-98.
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. |
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