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Early action potential shortening in hypoxic hearts: role of chloride current(s) mediated by catecholamine release.

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 degrees 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 (10 microM), the stilbenedisulfonic acid derivatives DIDS (10 microM) and SITS (1 mM), and diphenylamine-2 carboxylate (DPC, 100 microM) on action potential characteristics were determined at different times during hypoxia. The effect of chloride transport blockers on the outward currents induced by 200 nM carbonyl cyanide (CCCP) or by 1 microM isoproterenol 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 mM reproduced 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.

journal_name

J Mol Cell Cardiol

journal_title

Journal of molecular and cellular cardiology

authors

Ruiz Petrich E,Ponce Zumino A,Schanne OF

doi

10.1006/jmcc.1996.0026

subject

Has Abstract

pub_date

1996-02-01 00:00:00

pages

279-90

issue

2

eissn

0022-2828

issn

1095-8584

pii

S0022282896900267

journal_volume

28

pub_type

杂志文章

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