ORIGINAL ARTICLE

Pflügers Archiv

, Volume 435, Issue 3, pp 382-387

Effects of intracellular calcium on GABAA receptors in mouse cortical neurons

  • L. G. AguayoAffiliated withLaboratory of Neurophysiology, Department of Physiology, University of Concepcion, PO Box 152-C, Concepcion, Chile
  • , F. EspinozaAffiliated withLaboratory of Neurophysiology, Department of Physiology, University of Concepcion, PO Box 152-C, Concepcion, Chile
  • , G. KunosAffiliated withDepartment of Pharmacology and Toxicology, Medical College of Virginia, 410 North 12th St., Smith Bldg, Richmond VA 23298-0613, USA
  • , L. S. SatinAffiliated withDepartment of Pharmacology and Toxicology, Medical College of Virginia, 410 North 12th St., Smith Bldg, Richmond VA 23298-0613, USA

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Abstract

 Using the patch-clamp technique, we studied the effect of intracellular Ca2+ on Cl current gated by type A γ-aminobutyric acid receptors (GABAA) 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 μM). 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 μM vs. 7 ± 0.3 μM). Both calmodulin (CaM) and a CaM kinase II inhibitor (200 μM) blocked the potentiating effect of Ca2+ suggesting that it was mediated by activation of CaM kinase II. We found that regulation of GABAA 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 μM N-methyl-D-aspartate (NMDA). These findings suggest that modulation of GABAA receptor activity by glutamate may be brought about via changes in intracellular Ca2+.

Key words GABAA receptors Intracellular calcium Cortical neurons CaM kinase II Calmodulin Cl current Bicuculline NMDA