Stimulation of chloride in-->out permeation across the Deiters' neuron membrane by pentobarbital on the cytoplasmic side: additional evidence of GABA(A) receptors acting as chloride extrusion pumps.
Pentobarbital stimulates 36Cl- permeation across single Deiters' membranes in a microchamber system, acting on classical, extracellularly facing, GABA(A) receptors. However, when applied on the membrane cytoplasmic side it activates per se labeled chloride in-->out permeation. No effect was found on chloride out-->in permeation. Similarly, at lower concentrations it facilitates the increase of 36Cl- in-->out permeation by application of GABA on the membrane inside, again via asymmetric chloride channels allowing in-->out but not out-->in passage. These data confirm that on the Deiters' membrane cytoplasmic side there are structures behaving pharmacologically as GABA(A) receptors whose function is that of a Cl- extrusion pump. This mechanism involves a cycle of activation-phosphorylation/desensitization-reactivation of the receptor complexes.
Rapallino
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MV
Centro di Neurofisiologia Cerebrale, C.N.R., Genova, Italy.
Hydén
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Cupello
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D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism*; D003593:Cytoplasm; D018757:GABA Modulators / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D010424:Pentobarbital / Q000494:pharmacology*; D011817:Rabbits; D018079:Receptors, GABA / Q000502:physiology*; D003689:Vestibular Nucleus, Lateral / Q000187:drug effects / Q000648:ultrastructure*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D002712:Chlorides; D018757:GABA Modulators; D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid; D010424:Pentobarbital; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid