抄録
Ca2+-activated Cl− current (ICl(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 ICl(Ca) is modulated to affect action potential in normal or pathological conditions. In this study we examined the effects of external acidosis on ICl(Ca) and action potential. A whole-cell patch clamp was performed to record action potential and ICl(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 ICl(Ca) was increased at all membrane potentials. At pH 6.4, the apparent steady-state inactivation curves of ICl(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 ICl(Ca) was inhibited at low pH, early afterdepolarizations and triggered activities were induced. The amplitude of ICl(Ca) was suggested to be enhanced by the external acidosis, which may have prevented the induction of early afterdepolarization or triggered activity.
