Calcium movements in relation to heart function

Abstract

SumtnaryIt is widely recognized that calcium is of singular importance in the viability of the myocardial cell, nonetheless little is known concerning the precise nature of the action of calcium in myocardium as to how it maintains the life of the cell and how it may dictate the death of the cell. However, recent advances in research involved with the study of calcium movement in the heart have been highly valuable for the formulation of new concepts with respect to the physiological and pathological aspects of calcium metabolism in the myocardium. It is becoming clear that calcium movements are closely related to cardiac eleetrophysiological events, contractile function, membrane integrity and energy metabolism. In particular, a novel theory involving phosphatidylinositol turnover and Ca2+-dependent ATPase activation has been advanced regarding the mechanism and control of calcium entry into the cardiac cell upon excitation. Alterations in the regulation of calcium metabolism through the interaction of a number of separate elements may affect calcium distribution in the cell and thereby may change cardiac function and metabolism. The part calcium plays in the genesis of pathological states in the myoeardium is discussed in the light of research employing various experimental protocols. Intracellular calcium overload and deficiency are postulated to contribute to cardiac contractile failure and cell death through a number of distinct mechanisms. It is now a real challenge to understand the precise nature of processes associated with the occurrence of intracellular calcium overload or intracellular calcium deficiency in order to achieve proper management of cardiac disorders.

Alterations in phospholipid N-methylation of cardiac subcellular membranes due to experimentally induced diabetes in rats.

“…Since streptozotocin-induced diabetes in rats is associated with loss of body weight, it can be argued that the observed changes in cardiac phospholipid methylation are due to the catabolic effect of diabetes. Because our experiments with weight-matched as well as weight-and age-matched control animals showed values for the phospholipid methylation (26). The Ca2+ plus ATP-induced effect on phospholipid methylation was also seen in liver and skeletal muscle microsomes, where it was suggested to be mediated by a calmodulin-dependent regulatory system (24,25).…”

“…It has been shown that PE methyl transfer reaction starts on the cytoplasmic side of the membranes where cytosolic AdoMet is available to donate methyl groups (3). Therefore, in the beating heart cell, phospholipid methylation can be seen to occur in the presence of cytosolic levels of free Ca2" ranging from -lO-' M during rest to lO-' M in response to excitation (26). (l0-7 to l0-4 M) plus 10 ,gM ATP on the PE N-methylation activity at 0.055 ,uM AdoMet (site I, where PMME is specifically synthesized) in cardiac SL, SR, and mitochondria from control and diabetic hearts.…”

Oxygen free radicals and calcium homeostasis in the heart

“…The amount of Ca 2+ that enters the cell is a major determinant of the concentration of Ca z+ at the myofilaments during systole, and is a major determinant of the level of contactile force as a result [26]. In fact, ATP-independent Ca2 § in heart sarcolemma has been shown to exhibit linear relationship with the contaetile force development in the normal myocardium [24][25][26][27][28].…”

Alterations in Ca2+ binding by and composition of the cardiac sarcolemmal membrane in chronic diabetes.

“…Depressed Ca2' uptake by the sarcoplasmic reticulum as well as alterations in Ca2+-activated ATPase have been demonstrated for sarcoplasmic reticular and myofibrillar fractions from diabetic rat hearts (5,6). In view of the importance of the movement of extracellular Ca2+ across the myocardial membrane in modulating the contractile performance of the heart (7,8), it is possible that alterations in trans-sarcolemmal Ca2`flux may participate in this cardiomyopathy. This hypothesis has been indirectly supported by a preliminary study in which an abnormal response of isolated heart preparations from diabetic animals to extracellular Ca2' was found (9).…”