title: 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.affiliation: Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Tian
authors.initials: T
authors.lastname: Yu
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Kun
authors.initials: K
authors.lastname: Qian
authors.forename: Bu-Wei
authors.initials: BW
authors.lastname: Yu
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D059330:GABAergic Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D053444:Inhibitory Postsynaptic Potentials; D055369:Miniature Postsynaptic Potentials; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D011301:Preoptic Area / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043643:Receptor, Muscarinic M1 / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018686:Anesthetics, Intravenous; D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1; D010890:Pirenzepine; D005680:gamma-Aminobutyric Acid; D001285:Atropine; D015742:Propofol