EARLY ACTION-POTENTIAL SHORTENING IN HYPOXIC HEARTS - ROLE OF CHLORIDE CURRENT(S) MEDIATED BY CATECHOLAMINE RELEASE

We tested the hypothesis that the early action potential shortening in duced by hypoxia in perfused hearts is attributable to chloride curren ts activated or modulated by endogenous catecholamine release, Rabbit hearts perfused at 33 degrees C and paced at 2.5-2.8 Hz were used for membrane potential recordings with microelectrodes. Catecholamine depl etion was induced with reserpine treatment. The effects of nadolol (10 mu M), the stilbenedisulfonic acid derivatives DIDS (10 mu M) and SIT S (1 mM), and diphenylamine-2 carboxylate (DPC, 100 mu M) on action po tential characteristics were determined at different times during hypo xia, The effect of chloride transport blockers on the outward currents induced by 200 nM carbonyl cyanide (CCCP) or by 1 mu M isoproterenol in isolated cells was also tested, In control hearts, action potential duration (APD) at 25 and 95% repolarization decreased by 50 +/- 9% an d 32 + 7% respectively after 5 min of hypoxia, This effect was fully a ntagonized by reserpine pretreatment, by respiratory acidosis, and by nadolol when present from the beginning of hypoxia. None of these agen ts affected action potential characteristics in normoxia and nadolol h ad no effect when added after 15 min of hypoxia. Lowering the chloride concentration to 17.5 mM reproduced the effects of nadolol and reserp ine, DIDS and SITS lengthened APD in normoxia and attenuated the early APD shortening in hypoxia. DPC had no effect in normoxia but fully co unteracted APD shortening produced by isoproterenol or early hypoxia, In isolated cells, DIDS did not affect the glibenclamide sensitive out ward current induced by CCCP and DPC blocked the isoproterenol induced current, The data suggest that in whole hearts, chloride currents med iated by endogenous catecholamine release are involved in the early ac tion potential shortening induced by hypoxia with preservation of glyc olysis. (C) 1996 Academic Press Limited