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Science 18 August 1995:
Vol. 269. no. 5226, pp. 977 - 981
DOI: 10.1126/science.7638623
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Articles

Science, Vol 269, Issue 5226, 977-981
Copyright © 1995 by American Association for the Advancement of Science

articles

Ionic mechanisms of neuronal excitation by inhibitory GABAA receptors

KJ Staley, BL Soldo, and WR Proctor

Department of Neurology, University of Colorado Health Sciences Center, Denver 80262, USA.

Gamma-aminobutyric acid A (GABAA) receptors are the principal mediators of synaptic inhibition, and yet when intensely activated, dendritic GABAA receptors excite rather than inhibit neurons. The membrane depolarization mediated by GABAA receptors is a result of the differential, activity-dependent collapse of the opposing concentration gradients of chloride and bicarbonate, the anions that permeate the GABAA ionophore. Because this depolarization diminishes the voltage-dependent block of the N-methyl-D-aspartate (NMDA) receptor by magnesium, the activity-dependent depolarization mediated by GABA is sufficient to account for frequency modulation of synaptic NMDA receptor activation. Anionic gradient shifts may represent a mechanism whereby the rate and coherence of synaptic activity determine whether dendritic GABAA receptor activation is excitatory or inhibitory.


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Noninvasive Measurements of the Membrane Potential and GABAergic Action in Hippocampal Interneurons.
J. A. H. Verheugen, D. Fricker, and R. Miles (1999)
J. Neurosci. 19, 2546-2555
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Inhibitory Nature of Tiagabine-Augmented GABAA Receptor-Mediated Depolarizing Responses in Hippocampal Pyramidal Cells.
M. F. Jackson, B. Esplin, and R. Capek (1999)
J Neurophysiol 81, 1192-1198
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Synaptic Activation of GABAA Receptors Induces Neuronal Uptake of Ca2+ in Adult Rat Hippocampal Slices.
A.-M. Autere, K. Lamsa, K. Kaila, and T. Taira (1999)
J Neurophysiol 81, 811-816
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Interacting Appetite-Regulating Pathways in the Hypothalamic Regulation of Body Weight.
S. P. Kalra, M. G. Dube, S. Pu, B. Xu, T. L. Horvath, and P. S. Kalra (1999)
Endocr. Rev. 20, 68-100
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Interactions between Neuropeptide Y and {gamma}-Aminobutyric Acid in Stimulation of Feeding: A Morphological and Pharmacological Analysis.
S. Pu, M. R. Jain, T. L. Horvath, S. Diano, P. S. Kalra, and S. P. Kalra (1999)
Endocrinology 140, 933-940
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