Functional Consequences of Na/Ca Exchanger Overexpression in Cardiac Myocytes

Several factors are important in the relationship between Na/Ca exchanger overexpression and Ca cycling in physiological and pathophysiological situations. First, there are species differences. Transgenic mouse cardiac myocytes overexpressing Na/Ca exchanger showed a faster Ca transient associated with increased sarcoplasmic reticulum (SR) Ca content compared with wild-type myocytes. Cultured rabbit cardiac myocytes overexpressing Na/Ca exchanger showed reduced amplitude of the Ca transient and reduced SR Ca content. Second, the activity of other Ca regulatory proteins have to be considered. When Ca uptake via SR Ca ATPase (SERCA) was reduced by thapsigargin in transgenic mouse myocytes overexpressing Na/Ca exchanger, the time course of the Ca transient was slowed, and the SR Ca content was reduced to wild-type mouse myocyte levels, suggesting a potential compensatory role of Na/Ca exchanger overexpression when SERCA function is reduced. Finally, there are confounding factors related to the pathophysiological conditions. Our results suggest that Na/Ca exchanger overexpression can compensate for defects in SR Ca uptake in mouse myocytes. The consequences of Na/Ca exchanger overexpression in other species and conditions is unpredictable and require further investigation.