Insights into the activation mechanism of ρ1 GABA receptors obtained by coexpression of wild type and activation-impaired subunits

J. Amin, D. S. Weiss

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

To gain insight into the activation mechanism of homomeric ligand-gated receptor-channels, we examined human homomeric ρ1 GABA receptors with fewer than the normal number of agonist binding sites. This was accomplished by coexpressing different ratios of wild type and activation-impaired ρ1 subunits. Dose-response relations from oocytes coexpressing wild type and mutant subunits were comprised of two components in terms of GABA sensitivity; one 'wild type'-like and the other 'mutant'-like. Applying the binomial hypothesis to subunit coassembly enabled us to correlate these two components of the GABA dose-response relations to the underlying chimaeric receptor subtypes. We demonstrate that the receptors activate near normal provided that they are comprised of at least three wild type subunits. Our data are consistent with five equivalent and independent GABA binding sites of which only three need bind GABA to open the pore. The two additional binding sites may increase the GABA sensitivity of the ρ1 receptor and, when bound by agonist, stabilize the open state.

Original languageEnglish (US)
Pages (from-to)273-282
Number of pages10
JournalProceedings of the Royal Society B: Biological Sciences
Volume263
Issue number1368
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Environmental Science(all)
  • Agricultural and Biological Sciences(all)

Fingerprint Dive into the research topics of 'Insights into the activation mechanism of ρ<sub>1</sub> GABA receptors obtained by coexpression of wild type and activation-impaired subunits'. Together they form a unique fingerprint.

Cite this