Muscarinic M1 receptors regulate propofol modulation of GABAergic transmission in rat ventrolateral preoptic neurons.

Abstract	GABAergic neurons within the ventrolateral preoptic area (VLPO) play an important role in sleep-wakefulness regulation. Propofol, a widely used systemic anesthetic, has lately been reported to excite noradrenaline (NA)-inhibited type of VLPO neurons. Present study tested if acetylcholine system takes part in the propofol modulation of GABAergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) in mechanically dissociated rat VLPO neurons using a conventional whole-cell patch clamp technique. Propofol reversibly decreased mIPSC frequency without affecting the current amplitude, indicating that propofol acts presynaptically to decrease the probability of spontaneous GABA release. The propofol action on GABAergic mIPSC frequency was completely blocked by atropine, a nonselective muscarinic acetylcholine (mACh) receptor antagonist, and pirenzepine, a selective M1 receptor antagonist. These results suggest that propofol acts on M1 receptors on GABAergic nerve terminals projecting to VLPO neurons to inhibit spontaneous GABA release. The M1 receptor-mediated modulation of GABAergic transmission onto VLPO neurons may contribute to the regulation of loss of consciousness induced by propofol.
Authors	Yu Zhang, Tian Yu, Yang Liu, Kun Qian, Bu-Wei Yu
Journal	Journal of molecular neuroscience : MN (J Mol Neurosci) Vol. 55 Issue 4 Pg. 830-5 (Apr 2015) ISSN: 1559-1166 [Electronic] United States
PMID	25294312 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Anesthetics, Intravenous Muscarinic Antagonists Receptor, Muscarinic M1 Pirenzepine gamma-Aminobutyric Acid Atropine Propofol
Topics	Anesthetics, Intravenous (pharmacology) Animals Atropine (pharmacology) GABAergic Neurons (drug effects, metabolism, physiology) Inhibitory Postsynaptic Potentials Miniature Postsynaptic Potentials Muscarinic Antagonists (pharmacology) Pirenzepine (pharmacology) Preoptic Area (cytology, metabolism, physiology) Propofol (pharmacology) Rats Rats, Sprague-Dawley Receptor, Muscarinic M1 (metabolism) gamma-Aminobutyric Acid (metabolism)

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