Calcium: a mediator of the cellular response to chronic Na+/K(+)-ATPase inhibition

Chronic reduction of Na+/K(+)-ATPase activity has been demonstrated in a number of cell systems to elicit a cellular homeostatic response. Over the course of this response, there is initially a transient stimulation of synthesis of new Na+/K(+)-ATPase molecules, followed by a delayed decrease in its degradation rate, eliciting an effective increase in the number of active pumps in the membrane. The resultant enhancement of pumping capacity promotes the extrusion of accumulated Na+ ions and restores the intracellular electrolyte milieu to preinsult conditions. No cellular mediators of either component of this response have previously been described. We therefore tested the possibility that changes in [Ca2+]i might contribute to the transient stimulation of synthesis observed. Indeed, an effective synthetic response to the inhibition of Na+/K(+)-ATPase by treatment with ouabain required elevated [Ca2+]i levels.