Two types of gamma-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 gamma-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 muM) while baclofen, another analogue of GABA, produced only the change in APD (ED(50) = 1 muM). 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 muM.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.