Three high threshold calcium channel subtypes in rat corticotropes

In this study on highly enriched populations of cultured rat corticotropes, Ca2+ channel inhibitors were used to identify subtypes of the high threshold Ca2+ channel current under voltage clamp conditions. From a holding potential (-50 mV) that eliminated the low threshold T-type current, 52 +/- 4% of the total current in 10 mM Ba2+ was mediated by dihydropyridine-sensitive L-type Ca2+ channels. Blockade of this current was half-maximal at a nifedipine concentration of 187 nM. omega-Agatoxin-IVA (20 nM) maximally inhibited 28 +/- 3% of the total current. This high sensitivity to omega-agatoxin-IVA indicates that this noninactivating current is mediated by P-type Ca2+ channels. A very high threshold, noninactivating current (23 +/- 4% of the total Ba2+ current) remained after maximal inhibition of L- and P-type Ca2+ channels. This current was also resistant to toxins that inhibit N (omega-conotoxin-GVIA)- and Q (omega-conotoxin-MVIIC)-type Ca2+ channels. Because this current had slow activation kinetics and voltage dependence very different from those of the L- and P-type currents in these cells, it was probably mediated by a third unclassified Ca2+ channel subtype (or subtypes). It is concluded that the high threshold current in corticotropes is due to the presence of at least three different Ca2+ channel subtypes.