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

Hong Zhen Hu, Mei Shao, Zhi Wang Li

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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 EC50 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 EC50 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.

Original languageEnglish
Pages (from-to)883-890
Number of pages8
JournalNeuroscience
Volume89
Issue number3
DOIs
StatePublished - Mar 1999
Externally publishedYes

Keywords

  • Benzodiazepine
  • Dorsal root ganglion
  • GABA(A) receptor
  • Modulation
  • Muscarine
  • Pentobarbital

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