Referenced in: none

Automatically associated channels: Kv1.4 , Kv3.1 , Kv4.2 , Kv4.3

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

Authors: Gui-Rong Li, Xin-Ling Du, Yaw L Siow, Karmin O, Hung-Fat Tse, Chu-Pak Lau

Journal, date & volume: Cardiovasc. Res., 2003 Apr 1 , 58, 89-98

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12667949

Abstract
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.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.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.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.