Contribution of atp to oxidative stress -induced changes in the
action potential of isolated cardiac myocytes.
Bhatnagar, Aruni.
Departments of Physiology and Biophysics and Human Biological
Chemistry and Genetics, University of Texas Medical Branch, Galveston
TX 77555-1067
APStracts 3:0472H, 1996.
The role of ATP in oxidative stress-mediated changes in the cardiac
action potential was investigated in isolated adult rat cardiac
myocytes. Superfusion with H2O2 led to a decrease in the energy
charge, depletion of non-protein thiols, and elicited
hypercontracture of the myocytes. Treatment with 3-aminobenzamide (3
-AB), an inhibitor of protein ribosylation, increased the lifetime of
H2O2 -exposed myocytes, and attenuated depletion of ATP and non
-protein thiols. The H2O2 -mediated DNA stand breaks were increased in
the presence of 3-AB. Upon exposure to H2O2, myocytes patched clamped
with 1 mM ATP in the pipette, initially displayed prolonged action
potential durations (APD), which were later markedly abbreviated, and
accompanied by the activation of ATP-sensitive K& currents (IK
ATP). The late decrease in APD was inhibited by glibenclamide (which
inhibits IK ATP), but the initial prolongation of the action
potential was exacerbated. Treatment with 3-AB or recordings with 10
mM ATP in the patch pipette caused an initial delay in the expression
of H2O2-induced changes, but later caused a more pronounced and
sustained increase in APD. These interventions delayed the activation
of IK ATP. Thus, enhanced ribosylation (presumably due to activation
of DNA repair) appears to be a significant source of ATP depletion
under oxidative stress, which via activation of IK ATP, mediates
oxidative modifications in the action potential.
Received 7 May 1996; accepted in final form 1 October 1996.
APS Manuscript Number H410-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996