Regulation of voltage-dependent Ca²⁺ channels of neuronal cells by chronic changes in membrane potential

The regulation of voltage-dependent Ca²⁺ channels by chronic changes in membrane potential was studied by measuring the binding of [³H]nitrendipine to membranes from PC12 pheochromocytoma cells. Depolarization of the cells by elevation of extracellular K⁺ caused up to a 45% loss of [³H]nitrendipine binding sites within 4 days without any change in K_d. Repolarization of the cells caused a return to control binding within 1-2 days, showing that either decreases or increases in membrane potential can cause reversible changes in [³H]nitrendipine binding sites.