3 HIGH-THRESHOLD CALCIUM-CHANNEL SUBTYPES IN RAT CORTICOTROPES

In this study on highly enriched populations of cultured rat corticotr opes, Ca2+ channel inhibitors were used to identify subtypes of the hi gh threshold Ca2+ channel current under voltage damp conditions. From a holding potential(-50 mV) that eliminated the low threshold T-type c urrent, 52 +/- 4% of the total current in 10 mM Ba2+ was mediated by d ihydropyridine-sensitive L-type Ca2+ channels. Blockade of this curren t was half-maximal at a nifedipine concentration of 187 nM. omega-Agat oxin-IVA (20 nM) maximally inhibited 28 +/- 3% of the total current. T his high sensitivity to omega-agatoxin-IVA indicates that this noninac tivating current is mediated by P-type Ca2+ channels. A very high thre shold, noninactivating current (23 +/- 4% of the total Ba2+ current) r emained after maximal inhibition of L- and P-type Ca2+ channels. This current was also resistant to toxins that inhibit N (omega-conotoxin-G VIA)- and Q (omega-conotoxin-MVIIC)-type Ca2+ channels. Because this c urrent had slow activation kinetics and voltage dependence very differ ent from those of the L- and P-type currents in these cells, it was pr obably mediated by a third unclassified Ca2+ channel subtype (or subty pes). It is concluded that the high threshold current in corticotropes is due to the presence of at least three different Ca2+ channel subty pes.