title: Effects of riluzole on respiratory rhythm generation in the brainstem-spinal cord preparation from newborn rat.
abstract: The persistent sodium channel is an important pacemaker component in rhythm generation. In the present study, we examined the effects of a persistent sodium channel blocker, riluzole on pre-inspiratory (Pre-I) and inspiratory neurons in the rostral medulla as well as on 4th cervical ventral root (C4)-inspiratory activity in brainstem-spinal cord preparations. Preparations were isolated from postnatal day 0-3 Wistar rats and were superfused with artificial cerebrospinal fluid, equilibrated with 95% O2 and 5% CO2, pH 7.4, at 25-26 °C. The C4 inspiratory burst rate decreased in a dose-dependent manner (50-200 μM) after 15 min application of riluzole. Riluzole caused a strong reduction in the drive potential of Pre-I neurons but not of inspiratory neurons. After washout, C4 inspiratory burst gradually changed into an episodic pattern, in which one burst consisted of 3-9 short separate bursts. Riluzole also depressed the induction of repetitive firing induced by depolarizing stimulation. Under voltage clamp conditions, riluzole suppressed the negative-slope component of Pre-I neurons. Riluzole also depressed the intrinsic burst generation of Pre-I neurons in low calcium and high magnesium solution. Our findings indicate that the burst generation of Pre-I neurons is more sensitive than inspiratory burst generation to riluzole and thus suggested that persistent sodium channels have an important role in the burst generation of Pre-I neurons and are involved in the primary respiratory rhythm generation.
authors.affiliation: Department of Pharmacotherapeutics, Division of Clinical Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. Electronic address: mikiii0322@pharm.showa-u.ac.jp.
authors.forename: Shih Tien
authors.initials: ST
authors.lastname: Lin
authors.affiliation: Department of Physiology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. Electronic address: oni@med.showa-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Onimaru
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D009431:Neural Conduction / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010507:Periodicity; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects*; D019782:Riluzole / Q000494:pharmacology*; D013116:Spinal Cord / Q000502:physiology*; D013127:Spinal Nerves / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D019782:Riluzole
keywords: Burst generation; In vitro; Persistent sodium channels; Respiratory rhythm; Riluzole