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

• Published in: Neurochemical research 1999-03, Vol.24 (3), p.453-458
• Main Authors: Rapallino, M V, Hydén, H, Cupello, A
• Format: Article
• Language: English
• Subjects: 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid - pharmacology; Animals; Cell Membrane - drug effects; Cell Membrane - metabolism; Cell Membrane Permeability - drug effects; Chlorides - metabolism; Cytoplasm; GABA Modulators - pharmacology; gamma-Aminobutyric Acid - pharmacology; Male; Neurons - drug effects; Neurons - ultrastructure; Pentobarbital - pharmacology; Rabbits; Receptors, GABA - physiology; Vestibular Nucleus, Lateral - drug effects; Vestibular Nucleus, Lateral - ultrastructure
• ISSN: 0364-3190
• DOI: 10.1023/A:1020954120894

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.