Role of sodium ion gradient in facilitating extracellular calcium influx

The effect of extracellular Na+ on Ca++ influx in activated human platelets was evaluated with two methods. One method employed computer-aided subtraction of the time course of intracellular Ca++ changes in the absence of extracellular Ca++ from that observed in the presence of extracellular Ca++. The other utilized intracellular Ca++ elevation following the addition of Ca++ to a platelet suspension already activated by thrombin in the absence of extracellular Ca++. Both methods demonstrated that depletion of extracellular Na+ significantly attenuated Ca++ influx in activated platelets. That extracellular Na+ modifies the opening state of Ca++ channels was further substantiated with an experiment with Sr++ instead of Ca++. A flow cytometric study confirmed the validity of these experiments. Neither Na+/H+ exchange nor changes in the membrane potential appeared to be related to the effect of extracellular Na+ on Ca++ influx, and the mechanism by which extracellular Na+ permits Ca++ mobilization remains to be elucidated.