Allosteric modulation of GABAA receptors in acutely dissociated neurons of the suprachiasmatic nucleus

Masahiko Shimura; Nobutoshi Harata; Makoto Tamai; Norio Akaike

doi:10.1152/ajpcell.1996.270.6.C1726

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Allosteric modulation of GABAA receptors in acutely dissociated neurons of the suprachiasmatic nucleus

Journal article

Peer reviewed

Allosteric modulation of GABAA receptors in acutely dissociated neurons of the suprachiasmatic nucleus

Masahiko Shimura, Nobutoshi Harata, Makoto Tamai and Norio Akaike

The American journal of physiology, Vol.270(6 Pt 1), pp.C1726-1734

06/1996

DOI: 10.1152/ajpcell.1996.270.6.C1726

PMID: 8764156

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Abstract

The gamma-aminobutyric acid (GABA)-induced response was investigated in acutely dissociated suprachiasmatic nucleus (SCN) neurons of 11- to 14-day-old rats, under the voltage-clamp condition of nystatin-perforated patch recording. At a holding potential of -40 mV, application of GABA induced inward currents in a concentration-dependent manner. Pentobarbital and 5 beta-pregnan-3 alpha-ol-20-one (pregnanolone) similarly induced inward currents. GABA-induced inward currents were suppressed in a concentration-dependent manner by pretreating neurons with a GABAA receptor antagonist, bicuculline. Bicuculline (3 x 10(-6) M) shifted the concentration-response curve of GABA to the left in a competitive manner. Reversal potential of the GABA response (EGABA) was -3.4 +/- 0.7 mV, close to the theoretical Cl- equilibrium potential of -4.1 mV. Pretreating SCN neurons with diazepam, pentobarbital, and pregnanolone enhanced the 3 x 10(-6) M GABA response. Diazepam (3 x 10(-8) M), pentobarbital (3 x 10(-5) M), and pregnanolone (10(-7) M) shifted the concentration-response curve of GABA to the left without changing the maximal amplitude of GABA responses. EGABA in the presence of diazepam, pentobarbital, or pregnanolone was the same as that in their absence. These results show that the GABA response in acutely dissociated SCN neurons is mediated by the GABAA receptor. Because the GABAA receptor of SCN neurons is allosterically augmented by diazepam, pentobarbital, and pregnanolone, similarly as in other regions of the central nervous system, the present study opens up ways to functionally modulate the GABAA receptors in SCN.

Rats, Wistar

Allosteric Regulation

Pentobarbital - pharmacology

Rats

Male

Electric Conductivity

Bicuculline - pharmacology

Diazepam - pharmacology

GABA Antagonists - pharmacology

GABA-A Receptor Agonists

Animals

Pregnanolone - pharmacology

Chlorides - metabolism

Suprachiasmatic Nucleus - cytology

Receptors, GABA-A - physiology

Female

Suprachiasmatic Nucleus - metabolism

Neurons - metabolism

Receptors, GABA-A - metabolism

Intracellular Membranes - metabolism

Details

Title: Subtitle: Allosteric modulation of GABAA receptors in acutely dissociated neurons of the suprachiasmatic nucleus
Creators: Masahiko Shimura - Department of Physiology, Kyushu University Faculty of Medicine, Fukuoka, Japan
Nobutoshi Harata
Makoto Tamai
Norio Akaike
Resource Type: Journal article
Publication Details: The American journal of physiology, Vol.270(6 Pt 1), pp.C1726-1734
DOI: 10.1152/ajpcell.1996.270.6.C1726
PMID: 8764156
NLM abbreviation: Am J Physiol
ISSN: 0002-9513
eISSN: 2163-5773
Publisher: United States
Language: English
Date published: 06/1996
Academic Unit: Molecular Physiology and Biophysics
Record Identifier: 9984025432002771

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