Sodium-calcium exchange and calcium homeostasis in transfected Chinese hamster ovary cells

Our experiments with transfected cells provide new insights into the role of Na-Ca exchange activity in Ca homeostasis and emphasize the role of local interactions in determining exchanger function. Thus, the effects of ATP depletion and cytochalasin D highlight the influence of the actin cytoskeleton in regulating exchange activity. Cytoskeletal interactions could provide a mechanism for modulating exchange activity by mechanical stretch and might constitute a novel feedback mechanism for regulating contractile activity in the heart. The effects of Na on Ca entry during SDCI in the transfected cells suggest that local gradients of [Ca]i are important determinants of exchanger function. The surface distribution of exchanger proteins in relation to that of Ca channels therefore represents another area in which interactions with the cytoskeleton may be a central element in understanding the physiological function(s) of the exchange activity. At present, it seems likely that the exchanger's central hydrophilic domain mediates the connection between the exchanger and the cytoskeleton. This provides a rationale for understanding the importance of tissue-specific alterations in the exchanger's hydrophilic domain, which appear to have little affect on the kinetic behavior of the exchanger. Future work in our laboratory will be directed toward clarifying the role of cytoskeletal interactions in exchanger function.