• Shih Tien Lin and Hiroshi Onimaru.
• 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.
• Neurosci. Res. 2015 May 1; 94: 28-36.

AbstractThe 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.Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

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