Free radicals enhance na-ca exchange in ventricular myocytes.
Goldhaber, Joshua I., and James N. Weiss.
Department of Medicine (Cardiology) and the Cardiovascular Research
Laboratory, UCLA School of Medicine, Los Angeles, California
90095
APStracts 3:0036H, 1996.
Oxygen-derived free radicals (OFR) have been implicated in the
pathogenesis of intracellular calcium (Cai) overload and the
arrhythmias which characterize cardiac reperfusion. These arrhythmias
may in large part be due to activation of the pathological transient
inward current (ITI). However, the identity of the ITI generated by
OFR is uncertain. We previously found that hydrogen peroxide (H2O2),
an OFR generating compound, markedly stimulated the ITI elicited by
brief caffeine pulses in patch-clamped guinea pig ventricular
myocytes. In the present study, using patch clamped rabbit
ventricular myocytes loaded with the Ca2+-sensitive indicator Fura-2,
we have further characterized this ITI and have identified its major
component to be Na-Ca exchange, based on its dependence upon
extracellular Na and SR Ca2+ release, its sensitivity to Ni, and the
effects of its inhibition on relaxation. The effect on ITI was not
unique to H2O2 since another free radical generating system (FRGS),
xanthine + xanthine oxidase, produced a similar response. We
hypothesize that enhancement of Na-Ca exchange by OFR during
reperfusion, when intracellular Na is elevated, may promote Cai
overload and triggered arrhythmias.
Received 15 June 1995; accepted in final form 4 January 1996.
APS Manuscript Number H546-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 January 96