Pharmacological characterization of two calcium currents in GH3 cells

Whole cell patch-clamp techniques were used to investigate the pharmacological properties of calcium currents in the clonal rat pituitary cell line GH3. Current traces induced by a 100-ms pulse to 0 mV from a holding potential of -80 mV consisted of a component that rapidly inactivated during the pulse and a component that slowly inactivated during the pulse. When the holding potential was reduced to -32 mV, the rapidly inactivating component of the trace disappeared. The dihydropyridine calcium channel blocker nitrendipine affected only the slowly inactivating component of the trace. At a holding potential of -80 mV, nitrendipine blocked the slowly inactivating current with an IC50 of 1 microM. The IC50 for nitrendipine was found to be dependent on the holding potential, decreasing to 10 nM when the holding potential was -32 mV. The dihydropyridine agonist Bay-K 8644, like nitrendipine, affected only the slowly inactivating component. The inorganic blocker Cd2+ blocked both components but the slowly inactivating current was three- to fourfold more sensitive. These results are best explained by the existence of two types of calcium channels in these cells, one sensitive to dihydropyridines and one insensitive to dihydropyridines. These channels appear analogous to the T-type channel (inactivating current) and L-type channel (slowly inactivating current) described in other preparations.