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The effect of the oxidant hypochlorous acid on the L-type calcium current in isolated ventricular cardiomyocytes.

Abstract：

:Disturbances of cellular calcium homeostasis due to oxidative stress are involved in reperfusion associated phenomena like myocardial stunning and reperfusion induced arrhythmias. This study investigates the effect of the major neutrophil-derived oxidant hypochlorous acid (HOCl) on the l-type calcium current (ICa,L) of hamster ventricular cardiomyocytes. Using the whole-cell recording configuration of the patch-clamp technique, I Ca,L was recorded over 12.5 min (0.1 Hz). Application of HOCl or buffer (for control) via a second micropipette in close proximity to the cell was started at t=1 min. To study the influence of increased intracellular calcium buffer concentration and of ATP on HOCl-induced effects, internal solutions were composed as follows (EGTA/ATP in mmol/l): group I (standard) 0.5/0.0, group II 5.0/0.0, group III 0.5/1.0, and group IV 5.0/1.0. Application of 10, 20 and 40 micromol/l HOCl (under group I-conditions) caused a dose-dependent decrease in peak ICa,L to 82+/-3.2, 66+/-4.2 and 36+/-4.3% of baseline value (v 94+/-4.8% in controls, mean+/-s.e.m., P<0.05), and integrated ICa,L without affecting apparent reversal potential, activation and inactivation kinetics. HOCl-induced (40 micromol/l) decrease in ICa,L was partially inhibited in group II and III. Peak currents of these groups averaged 51+/-4.7 and 52+/-4.2% of baseline after 11.5 min administration of HOCl. Peak current in group IV cells decreased to 65+/-3.8% of baseline value (P<0.05 between group I-IV and v controls). Oxidative stress-induced decrease in ICa,L may be explained by energy depletion or calcium overload rather than by direct oxidative inactivation of channel proteins. A decrease in ICa, L may contribute to the shortening of action potential during reperfusion.

journal_name

J Mol Cell Cardiol

journal_title

Journal of molecular and cellular cardiology

authors

Hammerschmidt S,Wahn H

doi

10.1006/jmcc.1998.0749

subject

Has Abstract

pub_date

1998-09-01 00:00:00

pages

1855-67

issue

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(98)90749-0

journal_volume

pub_type

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The effect of the oxidant hypochlorous acid on the L-type calcium current in isolated ventricular cardiomyocytes.