Dihydropyridine block of omega-agatoxin IVA- 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 pharmacological properties of the high voltage-activated Ca2+ channels underlying these components are investigated with whole-cell recordings. We report that melanotropes express four pharmacologically distinct high voltage-activated Ca2+ channels. Non-inactivating L-type channels account for 35% of the total high voltage-activated channel population. These channels have a very high affinity for the dihydropyridine nimodipine (EC50 approximately 3 pM). The cone snail toxin omega-conotoxin GVIA irreversibly blocked an inactivating high voltage-activated component which accounted for 26% of the total whole-cell high voltage-activated Ca2+ current. The spider toxin omega-agatoxin IVA reversibly blocked an additional 31% of the total high voltage-activated current. The current blocked by omega-agatoxin IVA was not homogenous and consisted of a sustained component with a high affinity for omega-agatoxin IVA (< 10 nM) and an inactivating current with a low affinity for omega-agatoxin IVA (> 100 nM). Both the omega-agatoxin IVA and omega-conotoxin GVIA-blocked currents were very sensitive to nimodipine and nitrendipine with a half maximal block at 200-500 nM. 10 microM nimodipine blocked 70% of the omega-conotoxin GVIA-sensitive current and 90% of the omega-agatoxin IVA-sensitive current. Thus, omega-conotoxin GVIA- and omega-agatoxin IVA-sensitive high voltage-activated Ca2+ channels in melanotropes have an unusual high affinity for dihydropyridines compared to N-, P-, and Q-type channels in other preparations.
Mansvelder
H D
HD
Graduate School Neurosciences Amsterdam, Research Institute Neurosciences Vrije Universiteit, Faculty of Biology, Netherlands.
Stoof
J C
JC
Kits
K S
KS
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008547:Melanophores / Q000187:drug effects* / Q000378:metabolism; D009553:Nimodipine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000037:antagonists & inhibitors*; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013111:Spider Venoms / Q000037:antagonists & inhibitors*; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D009553:Nimodipine; C038806:1,4-dihydropyridine; D020866:omega-Conotoxin GVIA