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

Neurosci Lett. 2013 Sep 27;552:1-4. doi: 10.1016/j.neulet.2013.07.024. Epub 2013 Jul 26.


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.

Keywords: 5-HT(3) receptor; Breathing; Pulmonary sensory neurons; Volatile anesthetic.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Animals
  • Apnea / chemically induced
  • Apnea / physiopathology*
  • Biguanides / antagonists & inhibitors*
  • Isoflurane / administration & dosage
  • Isoflurane / pharmacology*
  • Lung / innervation
  • Lung / physiology
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Nerve Fibers, Unmyelinated / drug effects*
  • Nerve Fibers, Unmyelinated / physiology
  • Nodose Ganglion / drug effects
  • Nodose Ganglion / physiology
  • Rats
  • Serotonin 5-HT3 Receptor Agonists / pharmacology*
  • Serotonin 5-HT3 Receptor Antagonists / pharmacology


  • Biguanides
  • Serotonin 5-HT3 Receptor Agonists
  • Serotonin 5-HT3 Receptor Antagonists
  • Isoflurane
  • phenyl biguanide