Stoichiometry of a recombinant GABA(A) receptor

Yongchang Chang, Ruoping Wang, Sonal Barot, David S. Weiss

Research output: Contribution to journalArticle

356 Scopus citations

Abstract

GABA is the main inhibitory neurotransmitter in the mammalian brain. The postsynaptic GABA(A) receptor/pore complex is presumed to be a pentamer typically composed of a combination of α, β, and γ subunits, although the stoichiometry remains controversial. We probed the stoichiometry of the GABA(A) receptor by site-directed mutagenesis of a conserved leucine (to serine) in the putative second membrane-spanning domain of the rat α1(αL263S), β2(αL259S), and γ2(αL274S) subunit isoforms. Coexpression of wild-type and mutant subunits of each class (e.g., α and αL263S), along with their wild-type counterparts (e.g., β and γ), in Xenopus laevis oocytes resulted in mixed populations of receptors with distinct GABA sensitivities. This is consistent with the interpretation that the leucine mutation increased the GABA sensitivity in proportion to the number of incorporated mutant subunits. The apparent number of incorporated subunits for each class (α, β, and γ) could then be determined from the number of components comprising the compound GABA dose-response relationships. Using this approach, we conclude that the recombinant α1β2γ2 GABA(A) receptor is a pentamer composed of two α subunits, two β subunits, and one γ subunit.

Original languageEnglish (US)
Pages (from-to)5415-5424
Number of pages10
JournalJournal of Neuroscience
Volume16
Issue number17
StatePublished - Sep 1 1996
Externally publishedYes

Keywords

  • GABA
  • ion channel
  • mutagenesis
  • receptor
  • stoichiometry

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Chang, Y., Wang, R., Barot, S., & Weiss, D. S. (1996). Stoichiometry of a recombinant GABA(A) receptor. Journal of Neuroscience, 16(17), 5415-5424.