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KMID : 0869619850020020012
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Journal of Korean Society of Hospital Pharmacists
1985 Volume.2 No. 2 p.12 ~ p.31
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MYOCARDIAL CALCIUM TRANSPORT AND REGULATION
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Schwartz, Arnold
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Abstract
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The molecular mechanisms of myocardial contraction and relaxation and its intimate relationship to calcium can be readily understood in terms of the functions of membrane organelle and contractile protein systems. These systems include the sarcolemma, sarcoplasmic reticulum, mitochondria, and myofilaments. Such a regulatory function for these subcellular systems is attributed to their Ca^(2+) uptake and releasing properties and associated enzyme activities. In turn, specific regulatory proteins, such as phospholamban and calmodulin seem to be involved in mediating calcium transport functions of cell systems. The cardiac excitation-contraction coupling sequence then, is seen as reflections of a fluctuation in the intracellular-free Ca^(2+) concentration as well as possible changes in affinity of substrates for calcium. Therefore, it is clear that many Ca^(2+)-dependent processes can be targets for pharmacological agents such as the positive intropic drugs. Several examples of recently discovered positive inotropic agents are reviewed here. Evidence from studies on hemodynamic, pharmacological, electrophysiological and biochemical effects of these agents is presented. The implications of these results on the drugs´ mechanisms of action and, therefore, their ability to modulate Ca^(2+) transport pathways are discussed.
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KEYWORD
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