DIHYDROPYRIDINE BLOCK OF OMEGA-AGATOXIN IVA-SENSITIVE AND OMEGA-CONOTOXIN GVIA-SENSITIVE CA2+ CHANNELS IN RAT PITUITARY MELANOTROPIC CELLS

High voltage-activated Ca2+ currents in rat melanotropic cells consist of a sustained and an inactivating component. In this study the pharm acological properties of the high voltage-activated Ca2+ channels unde rlying these components are investigated with whole-cell recordings. W e report that melanotropes express four pharmacologically distinct hig h voltage-activated Ca2+ channels. Non-inactivating L-type channels ac count for 35% of the total high voltage-activated channel population. These channels have a very high affinity for the dihydropyridine nimod ipine (EC(50) similar to 3 pM). The cone snail toxin omega-conotoxin G VIA irreversibly blocked an inactivating high voltage-activated compon ent which accounted for 26% of the total whole-cell high voltage-activ ated Ca2+ current. The spider toxin omega-agatoxin IVA reversibly bloc ked an additional 31% of the total high voltage-activated current. The current blocked by omega-agatoxin IVA was not homogenous and consiste d of a sustained component with a high affinity for omega-agatoxin IVA (< 10 nM) and an inactivating current with a low affinity for omega-a gatoxin IVA (> 100 nM). Both the omega-agatoxin IVA and omega-conotoxi n GVIA-blocked currents were very sensitive to nimodipine and nitrendi pine with a half maximal block at 200-500 nM. 10 mu M nimodipine block ed 70% of the omega-conotoxin GVIA-sensitive current and 90% of the om ega-agatoxin IVA-sensitive current. Thus, omega-conotoxin GVIA- and om ega-agatoxin IVA-sensitive high voltage-activated Ca2+ channels in mel anotropes have an unusual high affinity for dihydropyridines compared to N-, P-, and Q-type channels in other preparations.