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TWO TYPES OF γ‐AMINOBUTYRIC ACID RECEPTOR ON EMBRYONIC SENSORY NEURONES
Author(s) -
DUNLAP KATHLEEN
Publication year - 1981
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1981.tb10467.x
Subject(s) - muscimol , bicuculline , baclofen , gabaa receptor , gaba receptor antagonist , endocrinology , chemistry , medicine , antagonist , receptor , gamma aminobutyric acid , gabab receptor , gaba receptor , stimulation , agonist , pharmacology , biology
1 Embryonic sensory neurones of the chick grown in dissociated cell culture respond to application of low concentrations of γ‐aminobutyric acid (GABA) with a change in resting membrane resistance (R in ) and/or a change in action potential duration (APD) (Dunlap & Fischbach, 1978; Choi & Fischbach, 1981). Intracellular microelectrode recording techniques were employed to determine if these two effects are mediated by the same, or different, GABA receptors. 2 Cells responded, for the most part, with a change in either R in or APD, but 10% of the cells exhibited both effects. In the latter cells the two responses were clearly distinguishable as discussed below. 3 The proportion of neurones exhibiting a GABA‐induced decrease in R in declined during the first week in vitro while the proportion exhibiting a decrease in APD increased during that time. 4 The two effects were pharmacologically distinct. Muscimol, a GABA analogue, produced only the change in R in (ED 50 = 5.5 μm) while baclofen, another analogue of GABA, produced only the change in APD (ED 50 = 1 μm). The analogues were approximately equipotent with GABA. Bicuculline, a GABA antagonist, blocked the muscimol‐induced change in R in (but not the baclofen‐induced change in APD) in a dose‐dependent fashion with an ID 50 = 0.7 μm. 5 The time courses of the two effects were different. The change in APD resulting from a brief application of GABA (or baclofen) was prolonged relative to the rapid return to control associated with the GABA‐ (or muscimol‐) induced change in R in . 6 Desensitization of the two responses exhibited separate time courses. In the continual presence of the agonists, GABA‐ and muscimol‐induced decreases in R in completely desensitized in ca. 10 s while GABA‐ and baclofen‐induced decreases in APD persisted undiminished throughout a prolonged (1 min) application of the drugs and returned to control only after cessation of application. 7 It is concluded that embryonic chick sensory neurones in culture exhibit two types of GABA receptor that differ in their functional and pharmacological properties. Implications of these results are discussed.