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).