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

Am J Physiol Heart Circ Physiol. 2002 Jul;283(1):H302-14. doi: 10.1152/ajpheart.00044.2002.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
  • 4-Aminopyridine / pharmacology
  • Animals
  • Calcium / metabolism*
  • Calcium / pharmacology
  • Cell Separation
  • Chloride Channels / drug effects
  • Chloride Channels / metabolism*
  • Chlorides / metabolism
  • Heart Ventricles / cytology
  • Heart Ventricles / drug effects
  • Heart Ventricles / metabolism*
  • In Vitro Techniques
  • Ion Transport / drug effects
  • Ion Transport / physiology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mice
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Niflumic Acid / pharmacology
  • Patch-Clamp Techniques
  • Potassium Channel Blockers / pharmacology
  • Tetraethylammonium / pharmacology

Substances

  • Chloride Channels
  • Chlorides
  • Potassium Channel Blockers
  • Niflumic Acid
  • Tetraethylammonium
  • 4-Aminopyridine
  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
  • Calcium