Early Action Potential Shortening in Hypoxic Hearts: Role of Chloride Current(s) Mediated by Catecholamine Release
Journal of Molecular and Cellular Cardiology(1996)
Abstract
We tested the hypothesis that the early action potential shortening induced by hypoxia in perfused hearts is attributable to chloride currents activated or modulated by endogenous catecholamine release. Rabbit hearts perfused at 33 °C and paced at 2.5 –2.8 Hz were used for membrane potential recordings with microelectrodes. Catecholamine depletion was induced with reserpine treatment. The effects of nadolol (10μm), the stilbenedisulfonic acid derivatives DIDS (10μm) and SITS (1 mm), and diphenylamine-2 carboxylate (DPC, 100μm) on action potential characteristics were determined at different times during hypoxia. The effect of chloride transport blockers on the outward currents induced by 200 nmcarbonyl cyanide (CCCP) or by 1μmisoproterenol in isolated cells was also tested. In control hearts, action potential duration (APD) at 25 and 95 % repolarization decreased by 50 ±9 % and 32 ±7 % respectively after 5 min of hypoxia. This effect was fully antagonized by reserpine pretreatment, by respiratory acidosis, and by nadolol when present from the beginning of hypoxia. None of these agents affected action potential characteristics in normoxia and nadolol had no effect when added after 15 min of hypoxia. Lowering the chloride concentration to 17.5 mmreproduced the effects of nadolol and reserpine. DIDS and SITS lengthened APD in normoxia and attenuated the early APD shortening in hypoxia. DPC had no effect in normoxia but fully counteracted APD shortening produced by isoproterenol or early hypoxia. In isolated cells, DIDS did not affect the glibenclamide sensitive outward current induced by CCCP and DPC blocked the isoproterenol induced current. The data suggest that in whole hearts, chloride currents mediated by endogenous catecholamine release are involved in the early action potential shortening induced by hypoxia with preservation of glycolysis.
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Key words
Hypoxia,Action potential shortening,Chloride currents,Anion transport blockers,Endogenous catecholamine release
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