Isoflurane inhibits bronchopulmonary C-fiber-mediated apneic response to phenylbiguanide by depressing 5-HT3 receptor function in anesthetized rats

A previous study by the authors has shown that isoflurane (ISO), a commonly used volatile anesthetic, has an excitatory effect on bronchopulmonary C-fibers (PCFs). Since selective stimulation of PCFs by action on local 5-HT3 receptors could evoke an apnea, this current study addresses whether inhalation of ISO would facilitate the PCF 5-HT3 receptor-mediated apneic response and, if so, how. In anesthetized and spontaneously breathing rats, inhalation of 5% ISO markedly inhibited the apneic response to intra-atrium injection of phenylbiguanide (PBG, 25 μg/kg), a 5-HT3 receptor agonist, which was contrary to the hypothesis. Extracellular recording of the nodose ganglion neurons in anesthetized, paralyzed and ventilated rats revealed that ISO attenuated the PBG-elicited excitation of pulmonary C neurons. Furthermore, using the patch clamp technique, it was found that ISO depressed the PBG-induced inward current of the pulmonary C neurons labeled with 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) instilled previously into the lungs. These results suggest that ISO inhibits PCF 5-HT3 channel functions, and thereby attenuates PCF excitatory response to PBG, likely contributing to the diminution of the PBG-induced apnea by ISO in rats.