The relationship between changes in intracellular ion concentrations and the antiarrhythmic effects of stilbene derivatives

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We investigated the possible role of CI<@D1-@>D1-HCO<@D3-(/)3@>D3 exchanger on ischemia-induced intracellular acidosis in isolated guinea pig ventricular muscle by measuring intracellular pH (pHi) and intracellular chloride (aC<@D1i@>D1l) with ion-selective microelectrode techniques. Stilbene derivatives, SITS and DIDS,were used as probes to block the CI<@D1-@>D1-HCO<@D3-(/)3@>D3 exchanger and their effects on action potentials (APs) , pHi and aC<@D1i@>D1l in ventricular muscles subjected to simulated ischemia were examined. Simulated ischmia was produced by stopping flow of superfusing solution and preparations were covered with mineral oil. Ischemia induced a progressive decrease in the maximum upstroke rate and resting membrane potentials, and shortened action potential duration, resulting in cessation of APs. SITS (0.5mM) and DIDS (0.1mM) delayd the onset of ischemia-induced deterioration of APs and prolonged the time to cessation of APs. Ischemia induced marked intracellular acido … More sis (pHi of control : 7.023(]SY.+-。[)0.083 ; pHi at 15 min after ischemia : 6.64(]SY.+-。[)0.012, n=6), and SITS or DIDS suppressed the development of intracellular acidosis during ischemia. There were significant differences in pHi change of SITS or DIDS-treated group at 10 and 15 min after ischemia compared with that of control group (p<0.05> . Under an external CI<@D1-@>D1-free condition, the time to cessation of APs during ischemia significantly delayd, and the acidification was suppressed. Furthermore, ischemia induced a great increase in aC<@D1i@>D1l (control : 18.74(]SY.+-。[)9.28mM ; ischemia : 55.3(]SY.+-。[)6.11mM] and this increase was suppressed by the external CI<@D1-@>D1-free or by stilbene derivatives. Present results indicate that activation of CI<@D1-@>D1-HCO<@D3-(/)3@>D3 exchanger is involved in the development of intracellular acidosis occurring during ischemia and that manipulation of pHi and aC<@D1i@>D1l by blocking CI<@D1-@>D1-HCO<@D3-(/)3@>D3 exchange by stilbene derivatives can attenuate ischemia-induced intracellular acidosis, thereby having beneficial effects on ischemia-induced arrhythmias. Less