Calcium transport systems in cardiac sarcolemma and their regulation by the second messengers cyclic AMP and calcium-calmodulin.
The purpose of this survey is to describe the importance of cyclic AMP and Ca2+-calmodulin as mediators of the effects of beta-adrenergic agonists on cardiac sarcolemma. First, the basic characteristics of the three sarcolemmal Ca2+-transporting systems, the slow Ca2+ channel, the Ca2+-pumping ATPase and the Na+/Ca2+ antiporter, are described. These different pathways for in- and outflux of Ca2+ play a crucial role in the excitation-contraction coupling and relaxation of heart muscle. Catecholamines in the myocardium cause an increase in the rate and extent of tension development during systole, and in the rate of relaxation during diastole. These functional changes may largely be brought about by cyclic AMP-induced phosphorylation of membrane proteins that increases both the probability of opening the slow Ca2+ channels and the rate of Ca2+ pumping ATPase. It is generally believed that the effects on Ca2+ transport systems are due to direct actions of beta-adrenergic agonists leading to an increased cytosolic Ca2+ level during systole. Indirectly, an increase in systolic Ca2+ can amplify the primary effect of catecholamine on the Ca2+ pumping ATPase and probably also on the Na+/Ca2+ antiporter through Ca2+-calmodulin-dependent phosphorylation of membrane proteins. The intimate involvement of calmodulin in the operation of several sarcolemmal Ca2+-transporting systems is discussed in the light of the unknown mechanism of action of the so-called Ca2+ channel blockers, a class of drugs that have a very important potential to provide information on the fundamental reaction steps in excitation-contraction coupling. Some of these drugs are potent inhibitors of Ca2+-calmodulin-regulated enzymes.
Lamers
J M
JM
D000251:Adenosine Triphosphatases / Q000502:physiology; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002147:Calmodulin / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation; D012508:Sarcolemma / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D013997:Time Factors
D002147:Calmodulin; D008565:Membrane Proteins; D012964:Sodium; D000242:Cyclic AMP; D000251:Adenosine Triphosphatases; D002118:Calcium