Enhancement of GABA-activated current by muscarine in rat dorsal root ganglion neurons

The modulation of GABA-gated ion channel responses to GABA, pentobarbital and diazepam by muscarine was studied in freshly isolated rat dorsal root ganglion neurons using a whole-cell patch-clamp technique. Muscarine enhanced current activated by 5 mu M GABA dose-dependently with an EC50 of 40 +/- 2 mu M. This potentiation was not blocked by pirenzepine, gallamine and atropine, the specific and non-specific muscarinic receptor antagonists. Muscarine shifted the GABA dose-response curve to the left, with the GABA EC50 decreased from 45 +/- 2 to 13 +/-2 mu M. The maximal response to GABA was suppressed to 89.3+/-4.6% as compared with the control (100%) by 80 mu M muscarine. Muscarine potentiated GABA (1-100 mu M)-activated current in a voltage-independent manner. Muscarine shifted the dose-response curve for pentobarbital enhancement of GABA-activated current to the left, and the enhancement of GABA-activated current by muscarine was additive to that of pentobarbital over all pentobarbital concentrations. Muscarine shifted the dose-response curve for diazepam (1-100nM) enhancement of GABA-activated current to the left. However, muscarine attenuated the facilitatory effect of saturating concentrations of diazepam (>100 nM). The potentiating effect of muscarine was blocked by 1 nM ethyl-beta-carboline-3-carboxylate, the inverse agonist of benzodiazepine receptors. These results suggest that GABA-gated ion channel responses to GABA and pentobarbital were potentiated by muscarine and the binding site(s) far muscarine might be related to those for diazepam. (C) 1999 IBRO. Published by Elsevier Science Ltd.