title: Effects of propofol on glycinergic neurotransmission in a single spinal nerve synapse preparation.
abstract: The effects of the intravenous anesthetic, propofol, on glycinergic transmission and on glycine receptor-mediated whole-cell currents (IGly) were examined in the substantia gelatinosa (SG) neuronal cell body, mechanically dissociated from the rat spinal cord. This "synaptic bouton" preparation, which retains functional native nerve endings, allowed us to evaluate glycinergic inhibitory postsynaptic currents (IPSCs) and whole-cell currents in a preparation in which experimental solution could rapidly access synaptic terminals. Synaptic IPSCs were measured as spontaneous (s) and evoked (e) IPSCs. The eIPSCs were elicited by applying paired-pulse focal electrical stimulation, while IGly was evoked by a bath application of glycine. A concentration-dependent enhancement of IGly was observed for ≥10µM propofol. Propofol (≥3µM) significantly increased the frequency of sIPSCs and prolonged the decay time without altering the current amplitude. However, propofol (≥3µM) also significantly increased the mean amplitude of eIPSCs and decreased the failure rate (Rf). A decrease in the paired-pulse ratio (PPR) was noted at higher concentrations (≥10µM). The decay time of eIPSCs was prolonged only at the maximum concentration tested (30µM). Propofol thus acts at both presynaptic glycine release machinery and postsynaptic glycine receptors. At clinically relevant concentrations (<1μM) there was no effect on IGly, sIPSCs or eIPSCs suggesting that at anesthetic doses propofol does not affect inhibitory glycinergic synapses in the spinal cord.
authors.affiliation: Research Division for Clinical Pharmacology, Medical Corporation, JyuryoGroup, Kumamoto Kinoh Hospital, 6-8-1 Yamamuro, Kitaku, Kumamoto 860-8518, Japan; Research Division for Life Science, Kumamoto Health Science University, 325 Izumi-machi, Kitaku, Kumamoto 861-5598, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Wakita
authors.affiliation: Research Division of Neurophysiology, Kitamoto Hospital, 3-7-6 Kawarasone, Koshigaya 343-0821, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kotani
authors.affiliation: Research Division for Clinical Pharmacology, Medical Corporation, JyuryoGroup, Kumamoto Kinoh Hospital, 6-8-1 Yamamuro, Kitaku, Kumamoto 860-8518, Japan; Research Division of Neurophysiology, Kitamoto Hospital, 3-7-6 Kawarasone, Koshigaya 343-0821, Japan; Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, Japan. Electronic address: akaike.n@juryo.or.jp.
authors.forename: Norio
authors.initials: N
authors.lastname: Akaike
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D005998:Glycine / Q000378:metabolism; D018684:Glycine Agents / Q000494:pharmacology*; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D018686:Anesthetics, Intravenous; D018684:Glycine Agents; D018009:Receptors, Glycine; D005998:Glycine; D015742:Propofol
keywords: Focal electrical stimulation; Glycine; Propofol; Spinal cord neuron; Synaptic neurotransmission; “Synaptic-bouton” preparation