CALCIUM TRANSIENTS IN STRIATED MUSCLE AND OTHER CELLS

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The calcium-sensitive bioluminescent protein aequorin and ion-selective microelectrodes will e used to study the regulation of intracellular Ca++ concentration in frog skeletal muscle, mammalian cardiac muscle, and certain other types of cells. High-gain image intensification will be used to localize Ca++ in aequorin-injected cells. Studies in skeletal muscle will be aimed primarily at understanding the regulation of [Ca++] in resting muscle, with particular emphasis on Na+-Ca++ exchange, and the roles of the sarcoplasmic reticulum and parvalbumin. The relation of resting [Ca++] to mechanical properties of resting muscle fibers will be explored. Studies in cardiac muscle will be directed at the determination of the relative importance of Ca++ entry and Ca++ release for excitation-contraction coupling in different types of heart muscle, and at differentiating the roles of changes in the amplitude of the Ca++ transient, in Ca++ uptake by the sarcoplasmic reticulum, and in the sensitivity of the contractile apparatus in the action of various physiological and pharmacological inotropic interventions. The results should increase our understanding of excitation-contraction coupling in both heart and skeletal muscle, and should facilitate a more rational design of drugs for the improvement of muscle function.