Channel opening locks agonist onto the GABA(C) receptor

Yongchang Chang, David S. Weiss

Research output: Contribution to journalArticlepeer-review

104 Scopus citations


Determination of the activation mechanism of neurotransmitter-operated ion channels has been hindered by a limited understanding of the relationship between agonist binding and the gating of the integral ion pore. Here we describe a [3H]ligand binding assay that enables us to make repeated binding measurements from the same intact oocyte expressing recombinant human ρl GABA(C) receptors and directly correlate the binding kinetics with electrophysiological measurements. We have determined an association rate for GABA of about 105 M-1s-1; this is four orders of magnitude slower than diffusion, indicating GABA has restricted access to its binding site. We also demonstrate that GABA dissociates at two rates. Our data are consistent with the faster rate being the true microscopic dissociation rate of GABA, with the slower rate occurring because the opening of the pore detains agonist release.

Original languageEnglish (US)
Pages (from-to)219-225
Number of pages7
JournalNature Neuroscience
Issue number3
StatePublished - Mar 1999
Externally publishedYes

ASJC Scopus subject areas

  • General Neuroscience


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