TWO TYPES OF γ‐AMINOBUTYRIC ACID RECEPTOR ON EMBRYONIC SENSORY NEURONES

Abstract

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 (ED₅₀ = 5.5 μm) while baclofen, another analogue of GABA, produced only the change in APD (ED₅₀ = 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 ID₅₀ = 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.