Anoxic contractile failure in rat heart myocytes is caused by failure of intracellular calcium release due to alteration of the action potential

M. D. Stern, H. S. Silverman, S. R. Houser, R. A. Josephson, M. C. Capogrossi, C. G. Nichols, W. J. Lederer, E. G. Lakatta

Research output: Contribution to journalArticle

Abstract

Anoxia of the heart causes failure of contraction before any irreversible injury occurs; the mechanism by which anoxia blocks cardiac excitation-contraction coupling is unknown. Studies in whole muscle are confounded by heterogeneity; however, achieving the low oxygen tensions required to study anoxia in a single myocyte during electrophysiological recording has been a barrier in experimental design. Guided by calculations of oxygen transport, we developed a system to insulate myocytes in an open dish from oxygen by a laminar counterflowing argon column, permitting free access to the cell by microelectrodes while maintaining a PO2 <0.02 torr (1 torr = 133 Pa). In the absence of glucose, the amplitude of stimulated contraction of anoxic ventricular myocytes fell to zero over 2 min after a lag period attributable to the consumption of endogenous glycogen. The cytosolic calcium concentration transient, measured by indo-1 fluorescence, fell to zero simultaneously with contraction. After the twich had failed, microinjection of caffeine around the cell still caused a large calcium release and contraction, indicating that sarcoplasmic reticular calcium stores were not depleted. Twitch failure was accompanied by shortening and then failure of the action potential; under voltage clamp, large outward currents, reversing at the resting potential, developed during contractile failure. After failure of action potential-mediated contraction, voltage-clamp depolarization, with a large command voltage to compensate for the series-resistance error due to outward currents, restored normal twitch contraction. We conclude that anoxic contractile failure in the rat myocyte is due to alteration of the action potential and the distal pathways of excitation-contraction coupling remain essentially intact.

Original languageEnglish (US)
Pages (from-to)6954-6958
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume85
Issue number18
DOIs
StatePublished - Jan 1 1988
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Anoxic contractile failure in rat heart myocytes is caused by failure of intracellular calcium release due to alteration of the action potential'. Together they form a unique fingerprint.

  • Cite this