Openings of cardiac atp-sensitive k+ channel by oxygen free
radicals generated by reactions between hypoxanthine and xanthine
oxidase.
Tokube, K., T. Kiyosue, and M. Arita.
Department of Physiology, Oita Medical University School of
Medicine, Hasama, Oita 879-55, Japan
APStracts 3:0043H, 1996.
We examined the effects of oxygen free radicals (OFRs) on action
potentials and membrane currents of guinea-pig ventricular myocytes.
OFRs produced biphasic changes in the action potential duration:
initial lengthening (30 sec after exposure to OFRs) and subsequent
shortening (within 5 min). In voltage clamp experiments, OFRs
suppressed the L-type calcium current (ICa,L), the delayed rectifier
K+ current (IK) and the inward rectifier K+ current (IK1). In
addition, OFRs increased the time-independent outward current
(Iterminal) at potentials > -30 mV. The increase in Iterminal
reflected activation of the ATP-sensitive K+ (KATP) channels as
glibenclamide (1 [mu]M) blocked this current. In inside-out patches,
OFRs significantly increased the open probability of the channel at a
relatively narrow range of ATP concentrations of 0.22 mM and this
effect was enhanced in the presence of ADP (0.1 mM) and abolished in
the presence of either free radical scavengers or glibenclamide.
These findings are compatible with the notion that OFRs activate KATP
channels by modulating ATP-binding sites of the KATP channels,
without affecting ADP-binding or glibenclamide-binding sites.
Received 5 October 1994; accepted in final form 5 January 1996.
APS Manuscript Number H893-4.
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