Allosteric modulation of gabaa receptors in acutely dissociated
neurons of the suprachiasmatic nucleus.
Shimura, Masahiko, Nobutoshi Harata, Makoto Tamai, and Norio Akaike.
Department of Physiology, Kyushu University Faculty of Medicine,
Fukuoka, JAPAN, Department of Ophthalmology, Tohoku University School
of Medicine, Sendai, JAPAN
APStracts 2:0410C, 1995.
The [gamma]-aminobutyric acid (GABA)-induced response was investigated
in the acutely dissociated suprachiasmatic nucleus (SCN) neurons of
the 11- to 14-day-old rats, under the voltage-clamp condition of the
nystatin-perforated patch recording. At a holding potential (VH) of
-40 mV, the 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.
The GABA-induced inward currents were concentration-dependently
suppressed by pretreating the neurons with a GABAA receptor
antagonist, bicuculline. Bicuculline (3x10-6 M) shifted the
concentration-response curve of GABA to the left in a competitive
manner. The reversal potential of GABA response (EGABA) was -3.4 +/-
0.7 mV, close to the theoretical Cl- equilibrium potential of -4.1
mV. Pretreating the SCN neurons with diazepam, pentobarbital and
pregnanolone enhanced the 3x10-6 M GABA response. Diazepam (3x10-8
M), pentobarbital (3x10-5 M) and pregnanolone (10-7 M) shifted the
concentration-response curve of GABA to the left without changing the
maximal amplitude of GABA responses. The 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 GABAA receptor. Since the
GABAA receptor of SCN neurons is allosterically augmented by
diazepam, pentobarbital and pregnanolone, similarly as in other
regions of the CNS, the present study will open up ways to
functionally modulate the GABAA receptors in SCN.
Received 27 March 1995; accepted in final form 16 November 1995.
APS Manuscript Number C169-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95