Relationship Between Cytosolic Free Calcium Ion Concentration and the Control of Pyruvate Dehydrogenase in Isolated Cardiac Myocytes and Synaptosomes
It is clear that the Ca2+ ion plays a central role in the mechanism of excitation-contraction coupling in muscle and in excitation-secretion coupling at the synapse (see, e.g. Katz, 1970; Rasmussen, 1981). What is perhaps not so well known is that in each case Ca2+ may also act as a signal to cause the activation of mitochondrial substrate oxidation. The increase in cytosolic free Ca2+ ([Ca2+]) on excitation of muscle cells activates actomyosin ATPase; the increase in [Ca2+] in a presynaptic nerve terminal upon depolarization triggers transmitter substance release, and occurs essentially at the same time as a decrease in the magnitude of Na+ and K+ -ion gradients, the latter requiring increased flux through the Na+ -K+ -ATPase for re-establishment. In each case, tissue activation is accompanied by increased utilization of ATP, with a consequently increased demand upon oxidative phosphorylation to re-synthesize ATP. It is the thesis of this article that Ca2+ acts as a signal to enhance mitochondrial substrate oxidation, so that energy supply and demand can be kept in balance.
KeywordsCardiac Myocytes Pyruvate Dehydrogenase Brain Mitochondrion Presynaptic Nerve Terminal Proton Electrochemical Gradient
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