Effects of intracellular calcium on GABA(A) receptors in mouse cortical neurons

Aguayo, L. G.; Espinoza F.; Kunos, G; Satin L.S.

Keywords: acid, enzyme, mouse, animals, conductivity, ion, brain, protein, cell, clamp, chloride, channel, gaba, calcium, mice, embryo, channels, receptor, agents, patch-clamp, methyl, level, nitro, inhibitors, article, kinase, ester, gating, calmodulin, bicuculline, techniques, controlled, animal, baclofen, current, study, 4, 3, priority, nonhuman, journal, gamma-Aminobutyric, Receptors,, dextro, a, aminobutyric, Cells,, Cultured, Inbred, Electric, patch, Chelating, Mice,, C57BL, 5, n, aspartic, dimethyl, dihydro, dependent, 1,4, 2,6, egtazic, glutamic, [2, (trifluoromethyl)phenyl], pyridinecarboxylic, N-Methylaspartate, Ca(2+)-Calmodulin

Abstract

Using the patch-clamp technique, we studied the effect of intracellular Ca2+ on Cl- current gated by type A ?-aminobutyric acid receptors (GABA(A)) in mouse cortical neurons. When the rapid Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) was in the pipette solution, the GABA-activated Cl- current amplitude decreased over time to 49 ± 7% of control. In contrast, equimolar replacement of BAPTA with ethylenebis(oxonitrilo)tetraacetate (EGTA) caused a 60 ± 10% increase in GABA current. An increased intracellular Ca2+ concentration caused a transient augmentation of the GABA current. This effect of Ca2+ was concentration dependent (10 nM to 34 ?M). Ca2+ increased the amplitude of the current by enhancing the maximal response to GABA rather than by changing the affinity of the receptor to GABA (EC50 = 5 ± 0.4 ?M vs. 7 ± 0.3 ?M). Both calmodulin (CaM) and a CaM kinase II inhibitor (200 ?M) blocked the potentiating effect of Ca2+ suggesting that it was mediated by activation of CaM kinase II. We found that regulation of GABA(A) receptors by intracellular Ca2+ in cortical neurons has important physiological implications since the potentiating effect of increasing the intracellular Ca2+ on responses to GABA was mimicked by activating excitatory receptors with 100 ?M N-methyl-D-aspartate (NMDA). These findings suggest that modulation of GABA(A) receptor activity by glutamate may be brought about via changes in intracellular Ca2+.

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Título de la Revista: PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
Volumen: 435
Número: 3
Editorial: Springer-Verlag
Fecha de publicación: 1998
Página de inicio: 382
Página final: 387
URL: http://www.scopus.com/inward/record.url?eid=2-s2.0-0031911039&partnerID=q2rCbXpz