title: Ionic mechanisms of neuronal excitation by inhibitory GABAA receptors.
abstract: 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.
authors.affiliation: Department of Neurology, University of Colorado Health Sciences Center, Denver 80262, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Staley
authors.forename: B L
authors.initials: BL
authors.lastname: Soldo
authors.forename: W R
authors.initials: WR
authors.lastname: Proctor
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D001639:Bicarbonates; D002712:Chlorides; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D000584:Amiloride; D008274:Magnesium; D000086:Acetazolamide