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

Abstract

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 μM GABA dose-dependently with an ec 50 of 40±2 μM. 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 ec 50 decreased from 45±2 to 13±2 μM. The maximal response to GABA was suppressed to 89.3±4.6% as compared with the control (100%) by 80 μM muscarine. Muscarine potentiated GABA (1–100 μM)-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 (1–100 nM) 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- β-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) for muscarine might be related to those for diazepam.