Intracellular chloride activity increases in guinea pig ventricular muscle during simulated ischemia

We investigated the effects of simulated ischemia on intracellular Cl− activity ([Cl−]i) in isolated guinea pig ventricular papillary muscles using ion-selective microelectrode techniques. Simulated ischemia in ventricular muscles was produced by stopping the flow of superfusion and immersing preparations in mineral oil as previously described [B. Vanheel, L. Leybaert, A. De Hemptinne, and I. Leusen. Am. J. Physiol. 257 ( Cell Physiol. 26): C365–C379, 1989; Z. F. Lai, J. Liu, and K. Nishi. Jpn. J. Pharmacol. 72: 161–174, 1996]. When preparations were exposed to paraffin oil for 15 min, [Cl−]imarkedly increased and the peak magnitude of [Cl−]ireached 55.3 ± 2.5 mM from 18.7 ± 3.5 mM, whereas membrane potentials ( V m) depolarized from −82.5 ± 1.1 to −54.7 ± 2.4 mV ( n = 6 muscles from 6 animals). SITS (0.5 mM), a known blocker of the Cl−/[Formula: see text]exchanger, suppressed the ischemia-induced depolarization of V m and delayed the onset of the ischemia-induced increase in [Cl−]ibut did not suppress the magnitude of the increase of [Cl−]i. Under Cl−-free conditions created by replacing Cl−with equimolar gluconate, the increase in [Cl−]iduring ischemia was transient and suppressed by >60% compared with that in normal-Cl− conditions (peak value was 20.3 ± 1.7 mM, n = 6 muscles from 6 animals). The present results provide direct evidence that [Cl−]iin ventricular muscle increases in ischemic conditions in quiescent guinea pig ventricular muscle, suggesting that activation of the Cl−/[Formula: see text]exchanger by ischemia would partially contribute to the elevation of [Cl−]iduring the initial stage of ischemia.