Zhong-Fang Lai, Jie Liu and Katsuhide Nishi (*)
Department of Pharmacology, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 860, Japan (*) To whom correspondence should be addressed.
Abstract: Using ion-selective microelectrode techniques, we investigated the effects of 4-acetamido- 4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS) and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), which are known as Cl--HCO3- exchange blockers, on action potentials and intracellular pH (pHi) in guinea pig ventricular papillary muscles subjected to simulated ischemia. Simulated ischemia was produced by stopping the flow of superfusing solution and then covering the preparations with mineral oil. Simulated ischemia induced a progressive decrease in the maximum upstroke rate and resting membrane potentials, shortened action potential duration, and resulted in cessation of action potentials within 10 - 12 min after the onset of simulated ischemia. The pHi-measurements revealed progressive intracellular acidosis during the period of simulated ischemia. SITS (0.5 mM) or DIDS (0.1 mM) delayed the onset of ischemia-induced deterioration of action potentials and prolonged the time to cessation of action potentials. SITS or DIDS (0.1 - 0.5 mM) induced an increase in pHi in HCO3--buffered solution and suppressed the development of intracellular acidosis during ischemia. Under the external Cl--free condition, the time to cessation of action potentials caused by ischemia was significantly delayed, and the development of intracellular acidosis during ischemia was attenuated. The present results indicate that activation of the Cl--HCO3- exchange system would be involved, in part, in the development of intracellular acidosis during cardiac ischemia.
Keywords:
Cl--HCO3- exchange, Simulated cardiac ischemia, Intracellular pH, Stilbene derivative,
Ion-selective microelectrode