Inhibition of rigor and of sarcoplasmic reticulum ca2+ cycling
enhances survival of adult rabbit ventricular myocytes subjected to
severe atp depletion.
Koyama, Takashi, David Boston, Hiroshi Ikenouchi, William H. Barry.
The Cardiology Division, University of Utah Medical Center, 50
North Medical Drive, Salt Lake City, Utah 84132
APStracts 3:0168H, 1996.
During severe ATP depletion, sarcolemmal rupture resulting from rigor
and/or Ca2+-induced myofilament force development are considered to
be important causes of irreversible cell injury. Recent experiments
in our laboratory demonstrated that during prolonged metabolic
inhibition in adult rabbit ventricular myocytes, in which rigor was
prevented by exposure to 30 mM 2,3-butanedione monoxime (BDM), cyclic
uptake and release of cystolic Ca2+ occurred, and was associated with
strong phasic contractions. To investigate the relative contribution
of this SR Ca2+ cycling and associated force development to energy
depletion injury, the effects of BDM together with 7 mM caffeine were
examined in isolated rabbit ventricular myocytes subjected to
metabolic inhibition with 2mM CN and 20mM 2-deoxyglucose (2-DG).
During 90 min. of metabolic inhibition with CN and 2-DG, no cells
retained a rod shape in the absence of BDM or caffeine. In the
presence of both 30 mM BDM and 7 mM caffeine during metabolic
inhibition, preservation of rod morphology was enhanced, and 52+6.2 %
of cells retained a rod shape 48 hours after metabolic inhibition,
and had normal ATP content and resting membrane potential. Both
systolic and diastolic function of cells that survived metabolic
inhibition, however, were impaired. We conclude that exposure to
caffeine together with BDM markedly enhances survival of myocytes
during severe prolonged ATP depletion. After recovery, these isolated
myocytes show some characteristics of stunning.
Received 3 April 1995; accepted in final form 8 December 1995.
APS Manuscript Number H316-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96