The low efficacy γ-aminobutyric acid type A agonist 5-(4- piperidyl)isoxazol-3-ol opens brief Cl- channels in embryonic rat olfactory bulb neurons
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The low efficacy γ-aminobutyric acid type A agonist 5-(4- piperidyl)isoxazol-3-ol opens brief Cl- channels in embryonic rat olfactory bulb neurons. / Kristiansen, U.; Barker, J. L.; Serafini, R.
In: Molecular Pharmacology, Vol. 48, No. 2, 1995, p. 268-279.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - The low efficacy γ-aminobutyric acid type A agonist 5-(4- piperidyl)isoxazol-3-ol opens brief Cl- channels in embryonic rat olfactory bulb neurons
AU - Kristiansen, U.
AU - Barker, J. L.
AU - Serafini, R.
PY - 1995
Y1 - 1995
N2 - 4-PIOL is a structural analog of GABA that has low efficacy at GABA(A), receptor Cl- channels and activates a nondesensitizing Cl- conductance in central neurons. We investigated the biophysical mechanisms of its low efficacy in embryonic olfactory bulb neurons, which express a limited number of GABA(A) 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 ~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 ~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.
AB - 4-PIOL is a structural analog of GABA that has low efficacy at GABA(A), receptor Cl- channels and activates a nondesensitizing Cl- conductance in central neurons. We investigated the biophysical mechanisms of its low efficacy in embryonic olfactory bulb neurons, which express a limited number of GABA(A) 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 ~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 ~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.
UR - http://www.scopus.com/inward/record.url?scp=0028981918&partnerID=8YFLogxK
M3 - Journal article
C2 - 7651360
AN - SCOPUS:0028981918
VL - 48
SP - 268
EP - 279
JO - Molecular Pharmacology
JF - Molecular Pharmacology
SN - 0026-895X
IS - 2
ER -
ID: 254466733