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 Ca(2+)-activated ionic currents. We studied the Ca(2+)-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 Ca(2+) dependent. The current is carried by Cl(-) and is critically dependent on Ca(2+) influx via voltage-gated Ca(2+) channels and the sarcoplasmic reticulum Ca(2+) 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 (approximately 1 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.
Xu
Yanfang
Y
Division of Cardiovascular Medicine, Department of Medicine, University of California, Davis, California 95616, USA.
Dong
Pei Hong
PH
Zhang
Zhao
Z
Ahmmed
Gias Uddin
GU
Chiamvimonvat
Nipavan
N
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002469:Cell Separation; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009544:Niflumic Acid / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology
D018118:Chloride Channels; D002712:Chlorides; D026902:Potassium Channel Blockers; D009544:Niflumic Acid; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium