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CHANGES IN CONTRACTION, CYTOSOLIC Ca2+ AND pH DURING METABOLIC INHIBITION AND UPON RESTORATION OF MITOCHONDRIAL RESPIRATION IN RAT VENTRICULAR MYOCYTES

Published online by Cambridge University Press:  03 January 2001

MATTHEW K. LANCASTER
Affiliation:
Department of Physiology, University of Leeds, Leeds LS2 9NQ, UK
SIMON M. HARRISON
Affiliation:
Department of Physiology, University of Leeds, Leeds LS2 9NQ, UK
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Abstract

Exposure of cardiac muscle to metabolic poisons reduces the availability of cellular ATP and cardiac dysfunction ensues. In this study rat ventricular myocytes were exposed to 2-deoxyglucose, iodoacetate and cyanide to induce complete metabolic blockade. Changes in contraction, cytosolic Ca2+ and pH were determined during metabolic blockade and following restoration of mitochondrial ATP production. Metabolic blockade resulted in a rapid failure of contractions and Ca2+ transients, a rise of diastolic Ca2+, a cytosolic acidosis and ultimately a rigor contracture. Washing out cyanide during the development of the rigor contracture led to a rapid relaxation of the contracture, a fall in cytosolic Ca2+ and a rapid, partial reversal of the cytosolic acidosis. The partial reversal of the cytosolic acidosis and fall of cytosolic Ca2+ were abolished in the presence of oligomycin. This suggests that the rapid partial recovery of cytosolic acidosis could result from the rephosphorylation of ADP to ATP by the mitochondrial F1,F0-ATPase (a reaction that consumes protons).

Type
Research Article
Copyright
© The Physiological Society 1998

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