Influence of mexiletine on action potential discharge and conduction in nodose Adelta afferent neurons innervating guinea pig isolated trachea.
Local anesthetics are among the most effective peripherally acting antitussives. A complete understanding of their pharmacological properties in airway afferent neurons associated with the cough reflex has been hampered by an incomplete understanding of the contribution of various classes of afferent neuron to cough. The aim of this study was to evaluate the influence of the antitussive local anesthetic mexiletine on nodose ganglion-derived vagal afferent Adelta-fibers innervating guinea pig trachea. This distinct subtype of airway sensory neuron was recently shown to be involved in evoking cough in anaesthetized guinea pigs. The current findings demonstrate that a concentration of mexiletine sufficient to inhibit citric acid- or mechanically-induced action potential initiation at the nerve ending did not block action potential conduction along axons. These findings are indicative of differences in sensitivity to local anesthetics of highly specialized regions of afferent neurons involved in initiation or conduction of impulses.
Carr
Michael J
MJ
UCB Research, Inc., 840 Memorial Drive, Cambridge, MA 02138, USA. michael.j.carr@gsk.com
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D019343:Citric Acid / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004594:Electrophysiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008801:Mexiletine / Q000494:pharmacology*; D009431:Neural Conduction / Q000187:drug effects* / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D009620:Nodose Ganglion / Q000187:drug effects* / Q000502:physiology; D010812:Physical Stimulation; D014132:Trachea / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D008801:Mexiletine; D019343:Citric Acid