Metabolic changes are critical in the regulation of Ca 2+ influx in central and peripheral neuroendocrine cells. To study the regulation of L-type Ca 2+ channels by AMPK we used biochemical reagents and ATP/glucose-concentration manipulations in rat chromaffin cells. AICAR and Compound-C, at low concentration, significantly induce changes in L-type Ca 2+ channel-current amplitude and voltage dependence. Remarkably, an overlasting decrease in the channel-current density can be induced by lowering the intracellular level of ATP. Accordingly, Ca 2+ channel-current density gradually diminishes by decreasing the extracellular glucose concentration. By using immunofluorescence, a decrease in the expression of Ca V 1.2 is observed while decreasing extracellular glucose, suggesting that AMPK reduces the number of functional Ca 2+ channels into the plasma membrane. Together, these results support for the first time the dependence of metabolic changes in the maintenance of Ca 2+ channel-current by AMPK. They reveal a key step in Ca 2+ influx in secretory cells.