RT Journal Article
SR Electronic
T1 The low efficacy gamma-aminobutyric acid type A agonist 5-(4-piperidyl)isoxazol-3-ol opens brief Cl- channels in embryonic rat olfactory bulb neurons.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 268
OP 279
VO 48
IS 2
A1 U Kristiansen
A1 J L Barker
A1 R Serafini
YR 1995
UL http://molpharm.aspetjournals.org/content/48/2/268.abstract
AB 4-PIOL is a structural analog of GABA that has low efficacy at GABAA receptor CI- channels and activates a nondesensitizing CI- conductance in central neurons. We investigated the biophysical mechanisms of its low efficacy in embryonic olfactory bulb neurons, which express a limited number of GABAA receptor subunit transcripts. Spectral analysis of GABA- and 4-PIOL-induced current fluctuations evoked in whole-cell recordings showed that three components with mean durations of approximately 0.7, 5, and 50 msec adequately describe the kinetics of the responses induced by both ligands. The contribution of the longest-lasting component was approximately 60% in the spectra of GABA-evoked responses but < 3% in the spectra of 4-PIOL-evoked responses. This is interpreted as a low incidence of long-lasting bursts in 4-PIOL-evoked responses. No difference was evident between the average inferred unitary conductances for 4-PIOL- and GABA-induced channels. These results at the level of the whole cell were confirmed and extended in outside-out single channel recordings. Taken together, the results indicate that the mechanism responsible for the low efficacy of 4-PIOL is the inability to produce frequent bursts of long duration.