Omega-conotoxin GVIA blocks a Ca2+ current in bovine chromaffin cells that is not of the "classic" N type.
Previous studies have identified two components of whole-cell Ca2+ current in bovine chromaffin cells. The "standard" component was activated by single depolarizations, while "facilitation" could be activated by large prepulses or repetitive depolarizations. Neither current component was sensitive to changes in holding potential between -100 and -50 mV; thus neither appeared to be carried by N-type Ca2+ channels. We now report that the facilitation Ca2+ current is insensitive to omega-conotoxin GVIA (omega-CgTx), but that the toxin blocks approximately 50% of the standard Ca2+ current. In some cells the toxin blocks all of the standard Ca2+ current, in others about half of the current, while in others it has no effect. Kinetic differences in current activation are observed after toxin application. These results suggest that the standard component of chromaffin cell Ca2+ current is composed of two pharmacologically distinct channels-one is omega-CgTx sensitive and the other is not. Two kinetically distinct types of 14 pS Ca2+ channels that may correspond to the omega-CgTx-sensitive and -insensitive components were observed in single-channel experiments. Because omega-CgTx blocked Ca2+ channels that were not inactivated by a depolarized holding potential, the commonly used Ca2+ channel categorization scheme may be inadequate to describe the Ca2+ channels found in chromaffin cells.
Artalejo
C R
CR
Department of Pharmacological and Physiological Sciences, University of Chicago, Illinois 60637.
Perlman
R L
RL
Fox
A P
AP
D000311:Adrenal Glands / Q000502:physiology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D002838:Chromaffin System / Q000502:physiology*; D004095:Dihydropyridines / Q000037:antagonists & inhibitors; D004553:Electric Conductivity; D008564:Membrane Potentials; D015737:Nisoldipine / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D010456:Peptides, Cyclic; D015737:Nisoldipine; C038806:1,4-dihydropyridine; D020866:omega-Conotoxin GVIA; D011188:Potassium