Assembly of GABAA receptor subunits: role of the delta subunit.
GABAA receptor channels (GABARs) composed of different combinations of rat alpha 1, beta 1, gamma 2L, and delta subunits were expressed transiently in mouse fibroblast cells (L929 cells). Whole-cell recordings were obtained from transfected cells to determine which combinations of GABAR subunits formed functional receptor channels, and to compare the electrophysiological and pharmacological characteristics of GABAR channels expressed in the presence and absence of the delta subunit. Only alpha 1 beta 1 gamma 2L, alpha 1 beta 1 gamma 2L delta, and alpha 1 beta 1 delta subunit combinations assembled to form functional GABAR channels and the presence of the delta-subunit slowed the rate of acute desensitization of GABA-evoked current during GABA application and the rate of recovery of GABA-evoked current following GABA application. These three different GABAR channel isoforms also showed distinct pharmacological profiles with differential sensitivity to block by zinc. Zinc was a potent blocker of alpha 1 beta 1 delta GABAR channels, a moderate-strength blocker of alpha 1 beta 1 gamma 2L delta GABAR channels, and did not block the alpha 1 beta 1 gamma 2L GABAR channels. These findings suggest that GABAR isoforms containing the delta subunit constitute a novel GABAR channel with distinct electrophysiological and pharmacological characteristics.
Saxena
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Department of Neurology, University of Michigan Medical School, Ann Arbor 48109-1687.
Macdonald
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D000818:Animals; D002460:Cell Line; D003975:Diazepam / Q000494:pharmacology; D004594:Electrophysiology; D005071:Evoked Potentials / Q000502:physiology; D005347:Fibroblasts; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D007811:Lanthanum / Q000494:pharmacology; D051379:Mice; D010424:Pentobarbital / Q000494:pharmacology; D010957:Plasmids; D051381:Rats; D011963:Receptors, GABA-A / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins; D015032:Zinc / Q000494:pharmacology
D007473:Ion Channels; D011963:Receptors, GABA-A; D011994:Recombinant Proteins; D007811:Lanthanum; D010424:Pentobarbital; D015032:Zinc; D003975:Diazepam