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Isoflurane (ISO) Inhibits Bronchopulmonary C‐fiber‐mediated Apneic Response to phenylbiguanide (PBG) by Depressing 5‐HT3 Receptor Function in Rats

Our previous study has shown that isoflurane (ISO), a commonly used volatile anesthetic, has an excitatory effect on bronchopulmonary C‐fibers (PCFs) (Zhang, et al., EB 2011, A377). Because right atrial bolus injection of PBG has been extensively used to selectively stimulate PCFs by action on local 5‐HT3 receptor, and thereby evoking an apnea, we asked whether inhalation of ISO would facilitate the PCF 5‐HT3 receptor‐mediated apneic response, and if so, how. Our experiments were performed in three groups of rats. We recorded the ventilatory response and pulmonary C neural response to right atrial bolus injection of PBG (25 μg/kg) before and during inhalation of 5% ISO. To this end, the ventilatory response was recorded in anesthetized and spontaneously breathing rats (Group I), while pulmonary C neurons were electrophysiologically isolated and extracellularly recorded in the nodose ganglion of anesthetized and paralyzed rats (Group II). Using perforated patch clamp technique in vitro, we further tested the effect of ISO (1 mM) on the PBG‐induced inward current of pulmonary C neurons labeled by previously instilling 1,1′‐dioctadecyl‐3,3,3′,3′‐tetramethylindocarbocyanine perchlorate (DiI) into the airways and lungs (Group III). Our results showed that inhalation of ISO markedly shortened the PBG‐produced apnea and attenuated the PBG‐elicited excitation of pulmonary C neurons. Moreover, ISO perfusion depressed the PBG‐induced inward current of pulmonary C neurons. These data suggest that ISO can inhibit PCF 5‐HT3 channel function to attenuate PCF excitatory response to PBG, likely contributing to shortening the PBG‐induced apnea by ISO in rats. (Supported by HL 107462 and ALA RG‐191095‐N)