Presence of a calcium-activated chloride current in mouse ventricular myocytes

The properties of several components of outward K+ currents, including the pharmacological and kinetics profiles as well as the respective molecular correlates, have been identified in mouse cardiac myocytes. Surprisingly little is known with regard to the Ca2+-activated ionic currents. We studied the Ca2+-activated transient outward currents in mouse ventricular myocytes. We have identified a 4-aminopyridine (4-AP)- and tetraethyl ammonium-resistant transient outward current that is Ca2+ dependent. The current is carried by Cl- and is critically dependent on Ca2+ influx via voltage-gated Ca2+ channels and the sarcoplasmic reticulum Ca2+ store. The current can be blocked by the anion transport blockers niflumic acid and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid. Single channel recordings reveal small conductance channels (similar to1 pS in 140 mM Cl-) that can be blocked by anion transport blockers. Ensemble-averaged current faithfully mirrors the transient kinetics observed at the whole level. Niflumic acid (in the presence of 4-AP) leads to prolongation of the early repolarization. Thus this current may contribute to early repolarization of action potentials in mouse ventricular myocytes.