title: Calcium-activated CL- current is enhanced by acidosis and contributes to the shortening of action potential duration in rabbit ventricular myocytes.
abstract: Ca2+-activated Cl- current (I(Cl(Ca))) is activated by Ca2+ transient via Ca2+-induced Ca2+ release from sarcoplasmic reticulum in cardiac myocytes and is supposed to play an important role in the repolarization of action potential. It is not well understood, however, how I(Cl(Ca)) is modulated to affect action potential in normal or pathological conditions. In this study we examined the effects of external acidosis on I(Cl(Ca)) and action potential. A whole-cell patch clamp was performed to record action potential and I(Cl(Ca)), using isolated rabbit ventricular myocytes. In the standard solution at pH 7.4, action potential duration (APD) was markedly prolonged by lowering the extracellular Cl- concentration ([Cl-](o)) or by applying an anion channel blocker, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). In the low pH solution at 6.4, APD was markedly shortened and the amplitude of I(Cl(Ca)) was increased at all membrane potentials. At pH 6.4, the apparent steady-state inactivation curves of I(Cl(Ca)) were shifted to more positive potentials compared with those at pH 7.4, but no change in inactivation occurred at a holding potential of -60 mV. The apparent activation curves were not changed between the two sets of conditions. When I(Cl(Ca)) was inhibited at low pH, early afterdepolarizations and triggered activities were induced. The amplitude of I(Cl(Ca)) was suggested to be enhanced by the external acidosis, which may have prevented the induction of early afterdepolarization or triggered activity.
authors.affiliation: Department of Cardiovascular Diseases, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, 113-8510 Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hirayama
authors.forename: Akinori
authors.initials: A
authors.lastname: Kuruma
authors.forename: Masayasu
authors.initials: M
authors.lastname: Hiraoka
authors.forename: Seiko
authors.initials: S
authors.lastname: Kawano
mesh_terms: D000138:Acidosis / Q000503:physiopathology*; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology; D002118:Calcium / Q000502:physiology*; D018118:Chloride Channels / Q000502:physiology*; D004553:Electric Conductivity; D006863:Hydrogen-Ion Concentration; D032383:Myocytes, Cardiac / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011817:Rabbits; D011930:Reaction Time / Q000502:physiology; D012016:Reference Values; D016276:Ventricular Function
chemical_list: D018118:Chloride Channels; D002118:Calcium