Na-Ca exchange in circulating blood cells.

The experiments with peripheral lymphocytes raise two provocative questions: is SDCI composed of Ca influx via both a Ca channel and Na-Ca exchanger?, and what is the role of Na-Ca exchange in lymphocytes? In regard to the first issue, the potential for this dual Ca influx pathway exists, inasmuch as both Ca store depletion (by exposure of cells to EGTA) and TG-treatment initiated Ca influx that was enhanced following reversal of the Na gradient. These data could be interpreted to suggest a role for Ca influx via the exchanger during lymphocyte activation. However, our ability to demonstrate Na-Ca exchange activity was facilitated by the removal of Ca sequestering or extrusion mechanisms, including SERCA Ca pumps and forward mode Na-Ca exchange. Thus, it seems likely that under physiological conditions the primary function of the exchanger is to mediate Ca efflux. In this regard, it might play a role in lymphocyte activation by limiting net Ca entry during the sustained phase of Ca mobilization. Since sustained Ca entry is critical for Ca-dependent processes including interleukin-2 production, exchange activity would be an important modulator of this process. Changes in membrane potential, intracellular [Na] and cytosolic pH could therefore regulate Cai through its effects on Na-Ca exchange activity. Future challenges include defining the role of the Na-Ca exchange in Cai homeostasis and characterizing its function in lymphocyte populations.