title: Propofol-induced spike firing suppression is more pronounced in pyramidal neurons than in fast-spiking neurons in the rat insular cortex.
abstract: Propofol is a major intravenous anesthetic that facilitates GABAAreceptor-mediated inhibitory synaptic currents and modulates inward current (Ih), K+, and voltage-gated Na+currents. This propofol-induced modulation of ionic currents changes intrinsic membrane properties and repetitive spike firing in cortical pyramidal neurons. However, it has been unknown whether propofol modulates these electrophysiological properties in GABAergic neurons, which express these ion channels at different levels. This study examined whether pyramidal and GABAergic neuronal properties are differentially modulated by propofol in the rat insular cortical slice preparation. We conducted multiple whole-cell patch-clamp recordings from pyramidal neurons and from GABAergic neurons, which were classified into fast-spiking (FS), low threshold spike (LTS), late-spiking (LS), and regular-spiking nonpyramidal (RSNP) neurons. We found that 100μM propofol hyperpolarized the resting membrane potential and decreased input resistance in all types of neurons tested. Propofol also potently suppressed, and in most cases eliminated, repetitive spike firing in all these neurons. However, the potency of the propofol-induced changes in membrane and firing properties is particularly prominent in pyramidal neurons. Using a low concentration of propofol clarified this tendency: 30μM propofol decreased the firing of pyramidal neurons but had little effect on GABAergic neurons. Pre-application of a GABAAreceptor antagonist, picrotoxin (100μM), diminished the propofol-induced suppression of neural activities in both pyramidal and FS neurons. These results suggest that GABAergic neurons, especially FS neurons, are less affected by propofol than are pyramidal neurons and that propofol-induced modulation of the intrinsic membrane properties and repetitive spike firing are principally mediated by GABAAreceptor-mediated tonic currents.
authors.affiliation: Department of Anesthesiology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kaneko
authors.affiliation: Department of Anesthesiology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan; Division of Immunology and Pathobiology, Dental Research Center, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Koyanagi
authors.affiliation: Department of Anesthesiology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan; Division of Immunology and Pathobiology, Dental Research Center, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Oi
authors.affiliation: Department of Pharmacology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan; Division of Oral and Craniomaxillofacial Research, Dental Research Center, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan; RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: kobayashi.masayuki@nihon-u.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D059330:GABAergic Neurons / Q000187:drug effects* / Q000502:physiology; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D015742:Propofol / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D055647:Rats, Transgenic; D011963:Receptors, GABA-A / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: D006993:Hypnotics and Sedatives; D011963:Receptors, GABA-A; D015742:Propofol
keywords: GABAergic; anesthetics; interneurons; nociception; tonic current