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 microM GABA dose-dependently with an EC50 of 40 +/- 2 microM. 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 microM. The maximal response to GABA was suppressed to 89.3 +/- 4.6% as compared with the control (100%) by 80 microM muscarine. Muscarine potentiated GABA (1-100 microM)-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-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) for muscarine might be related to those for diazepam.
Hu
H Z
HZ
Research Center of Experimental Medicine, Tongji Medical University, Wuhan, The People's Republic of China.
Shao
M
M
Li
Z W
ZW
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology*; D005703:Gallamine Triethiodide / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects*; D015640:Ion Channel Gating; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D009116:Muscarine / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000502:physiology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010424:Pentobarbital / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D002243:Carbolines; D018755:GABA Agonists; D018757:GABA Modulators; D007473:Ion Channels; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D009419:Nerve Tissue Proteins; D018733:Nicotinic Antagonists; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D005680:gamma-Aminobutyric Acid; C024915:beta-carboline-3-carboxylic acid ethyl ester; D001285:Atropine; D009116:Muscarine; D002217:Carbachol; D010424:Pentobarbital; D000109:Acetylcholine; D005703:Gallamine Triethiodide; D003975:Diazepam; D001640:Bicuculline