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Titolo:
PROTON MODULATION OF FUNCTIONALLY DISTINCT GABA(A) RECEPTORS IN ACUTELY ISOLATED PYRAMIDAL NEURONS OF RAT HIPPOCAMPUS
Autore:
PASTERNACK M; SMIRNOV S; KAILA K;
Indirizzi:
UNIV HELSINKI,DEPT BIOSCI,DIV ANIM PHYSIOL,POB 17 FIN-00014 HELSINKI FINLAND
Titolo Testata:
Neuropharmacology
fascicolo: 9-10, volume: 35, anno: 1996,
pagine: 1279 - 1288
SICI:
0028-3908(1996)35:9-10<1279:PMOFDG>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
METHYL-D-ASPARTATE; CENTRAL-NERVOUS-SYSTEM; A RECEPTORS; SYNAPTIC TRANSMISSION; SUBUNIT COMPOSITION; INTRACELLULAR PH; CHANNEL FUNCTION; PATCH-CLAMP; SUBTYPES; SLICES;
Keywords:
GABA(A) RECEPTOR; PH; ZINC; RAT; HIPPOCAMPUS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
47
Recensione:
Indirizzi per estratti:
Citazione:
M. Pasternack et al., "PROTON MODULATION OF FUNCTIONALLY DISTINCT GABA(A) RECEPTORS IN ACUTELY ISOLATED PYRAMIDAL NEURONS OF RAT HIPPOCAMPUS", Neuropharmacology, 35(9-10), 1996, pp. 1279-1288

Abstract

We have studied the effect of extracellular pH (pH(o)) on the GABA(A)receptor-mediated chloride conductance in acutely isolated pyramidal neurons from area CA1 of the rat hippocampus under whole-cell voltage clamp in bicarbonate-free solutions. The conductance evoked by saturating or near-saturating concentrations (200-1000 mu M) of GABA showed amarked sensitivity to variations of pH(o) around 7.4. A decrease in pH(o) between 8.4 and 6.4 increased the GABA(A) receptor-mediated chloride conductance by about two-fold per pH unit. In contrast, when evoked by a low agonist concentration (1-10 mu M) the conductance showed anequally marked decrease upon a decrease in pH(o). The half-time for desensitization of the conductance induced by 500 mu M GABA was around 900 ms at pH(o) 6.4 and 7.4, but decreased to 650 ms at pH(o) 8.4. A fall in pH(o) decreased the amount of desensitization of the conductance evoked by a 5 s application of 5 mu M, but not of 500 mu M, GABA. The concentration-response relationship of the GABA-induced conductance showed a local plateau between 50 and 100 mu M of GABA, which was particularly evident at high pH(o). Assuming two receptor populations witha high and a low affinity for GABA, the effect of H+ on the GABA(A) receptors could be explained as an increase in the EC(50) of the high affinity receptor, and an apparently noncompetitive potentiation of both the high and the low affinity receptors. The GABA(A) receptor-mediated conductance was markedly inhibited by 20-50 mu M Zn2+. In addition,Zn2+ reverted the down-modulation by H+ observed at low GABA concentrations to up-modulation. Diazepam (1-10 mu M) had only a marginal effect on the GABA-gated conductance. Taken together, the results suggest the coexistence in individual hippocampal neurons of two distinct GABA(A) receptor populations having differential sensitivities to H+. In the light of the inhibitory action of Zn2+ and the virtual absence of an effect of diazepam it is probable that a significant fraction of theGABA(A) receptors lack the gamma(2) subunit. The observation that an elevated pH has a strong suppressing effect on the conductance evoked by high concentrations of GABA may at least partly explain why an extracellular alkalosis leads to neuronal hyperexcitability. Copyright (C)1996 Elsevier Science Ltd.

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Documento generato il 28/11/20 alle ore 11:07:22