Introduction

The heart has long been a popular model for study of Sodium-Calcium Exchange in the Cardiovascular System. Much emphasis at the conference was placed on the controversial role of Na+-Ca2+ exchange as a Ca2+ influx mechanism in the cardiac tissue. Investigators agree that Na+-Ca2+ exchange is the dominant Ca2+ efflux mechanism of the myocardium. Experiments on the role of exchange as a Ca2+ trigger mechanism, however, have had conflicting results. Clearly, the exchanger can induce Ca2+ release from the sarcoplasmic reticulum under nonphysiologic conditions, but the physiologic significance is unclear. Large intracellular Ca2+ gradients can exist in myocytes due to the geometry of the diadic cleft region. Modeling of Ca2+ fluxes in the cleft region indicate that Ca2+ gradients are an integral part of the excitation-contraction coupling process. Possibly, localization of the exchanger in specific domains of the sarcolemma influences the excitation-contraction coupling process. Pharmacological and other interventions have been used to separate the relative roles of sarcoplasmic reticular and sarcolemmal Ca2+ fluxes in the contractile process. These experiments indicate that about 20% of the coupling Ca2+ is extruded from the cell by the exchanger following each contraction. Antibodies and DNA probes for the exchanger have been used to examine exchanger levels in different situations. Strikingly, the exchanger is upregulated in the myocardium during the fetal and neonatal periods. Likewise, exchanger transcript levels are elevated during the initial phase of induced hypertrophy. The fate of the exchanger during other myopathies is also being examined.