AMPK Inhibits Voltage-gated Calcium Channel-current in Rat Chromaffin Cells

Metabolic changes are critical in the regulation of Ca influx in central and peripheral neuroendocrine cells. To study the regulation of L-type Ca 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 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 channel-current density gradually diminishes by decreasing the extracellular glucose concentration. By using immunofluorescence, a decrease in the expression of Ca1.2 is observed while decreasing extracellular glucose, suggesting that AMPK reduces the number of functional Ca channels into the plasma membrane. Together, these results support for the first time the dependence of metabolic changes in the maintenance of Ca channel-current by AMPK. They reveal a key step in Ca influx in secretory cells.