Does glial uptake affect GABA responses? AN intracellular study on rat dorsal root ganglion neurones in vitro.

1. Using single barrel pipettes, intracellular records were obtained from surface neurones of isolated rat dorsal root ganglia (DRG) impaled under microscopic vision.2. Responses to gamma-aminobutyric acid (GABA) were elicited either by ionophoresis or by placing drops of concentrated GABA solutions directly into the flow of superfusing Ringer. Using this latter method it was estimated that the GABA concentration eliciting threshold ( approximately 1 mV) responses was 3-20 muM.3. Short (</= 1 sec) ionophoretic or drop administrations of GABA elicited depolarizing responses associated with an increased membrane conductance. With longer applications the initial depolarization was not sustained but decayed to a lower plateau level (desensitization) associated with a minimal conductance change.4. Low chloride superfusions did not affect subsequent responses to GABA unless GABA was also administered during the low chloride superfusion, in which case responses declined markedly. This suggests that GABA caused appreciable chloride fluxes when it was administered regularly (e.g. for 1 sec every minute).5. Glial GABA uptake was inhibited by adding 1 mM-beta-alanine or 0.25 mM-chlorpromazine to the bicarbonate-Ringer superfusate or by substituting lithium for sodium in a Tris-Ringer superfusate. Uptake inhibition had no consistent effect on any of the parameters studied, namely membrane potential, input resistance, amplitude and time course of responses to GABA, and GABA desensitization.6. Muscimol and isoguvacine, which are probably not substrates for the glial GABA carrier, elicited responses with time course and desensitization characteristics indistinguishable from those of responses to GABA.7. GABA superfused at concentrations as low as 1 muM could reduce responses to ionophoretic GABA, i.e. cause a desensitization of GABA receptors.8. It is concluded firstly that in DRG, glial uptake does not affect the amplitude or time course of responses to GABA when the neurone under study is close to the source of GABA; and secondly that desensitization can occur independently of GABA uptake.9. The findings are discussed in relation to their possible relevance to GABA systems in the central nervous system.