GABAA Receptor-Mediated Chloride Currents in Acutely Dissociated Hippocampal Neurons
γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter substance in the central nervous system of practically all multicellular animals (Kaila 1994; Michelson and Wong 1991). The endogenous ligand GABA binds to two fundamentally different classes of receptors, GABAA and GABAB. Despite their common sensitivity for GABA the two receptors are completely different in their sensitivity to agonists and antagonists. The classical GABA-gated receptors, or GABAA receptors, are sensitive to the agonist muscimol and blocked by picrotoxin or bicuculline. GABAA is a ligand-gated ion channel which is composed of several distinct polypeptide units, forming together a hetero-oligometric protein molecule with a specific conductance for chloride. GABAB receptors, by contrast, were found to respond to baclophen as an agonist and to be blocked by 2OH-saclophen or phaclophen. GABAB receptors are functionally coupled to certain K+ and Ca2+ channels through GTP-binding proteins and/or other second messenger systems. Both receptors are interesting from a clinical point of view. Modulation of GABAB receptors by baclophen was shown to ameliorate the spasticity so common in paraplegic patients. GABAA receptor modulation was extensively studied in relation to sleeping disorders, epilepsy and anesthesia. An excellent introduction to the subject is given by Macdonald and Olsen (1994) and Kaila (1994).
KeywordsGABAA Receptor Razor Blade GABAB Receptor Pipette Solution Extracellular Solution
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