ATP SERVES AS A NEGATIVE FEEDBACK INHIBITOR OF VOLTAGE-GATED CA2+ CHANNEL CURRENTS IN CULTURED BOVINE ADRENAL CHROMAFFIN CELLS

Modulation of voltage-gated Ca2+ channel current (I-Ca) regulates secr etion of catecholamines from adrenal chromaffin cells. Previous work d emonstrated that I-Ca can be augmented by phosphorylation to increase secretion or that inhibition of I-Ca results in diminished catecholami ne secretion. In the current manuscript, we show that stimulation of c hromaffin cells results in the release of an ''endogenous inhibitor'' that suppresses I-Ca. The inhibition is due to the secretion of ATP, w hich is stored at high concentrations in secretory granules and is cor eleased with catecholamines upon stimulation. The ATP exerts its actio ns through P-2Y purinoceptors and inhibits both N- and P/Q-type Ca2+ c hannels in a voltage-dependent manner but with different efficacies. O verall, we have identified and characterized a negative feedback pathw ay that may serve as an important regulatory mechanism for catecholami ne secretion in chromaffin cells.