Isoflurane depolarizes bronchopulmonary C neurons by inhibiting transient A-type and delayed rectifier potassium channels.
Inhalation of isoflurane (ISO), a widely used volatile anesthetic, can produce clinical tachypnea. In dogs, this response is reportedly mediated by bronchopulmonary C-fibers (PCFs), but the relevant mechanisms remain unclear. Activation of transient A-type potassium current (IA) channels and delayed rectifier potassium current (IK) channels hyperpolarizes neurons, and inhibition of both channels by ISO increases neural firing. Due to the presence of these channels in the cell bodies of rat PCFs, we determined whether ISO could stimulate PCFs to produce tachypnea in anesthetized rats, and, if so, whether this response resulted from ISO-induced depolarization of the pulmonary C neurons via the inhibition of IA and IK. We recorded ventilatory responses to 5% ISO exposure in anesthetized rats before and after blocking PCF conduction and the responses of pulmonary C neurons (extracellularly recorded) to ISO exposure. ISO-induced (1mM) changes in pulmonary C neuron membrane potential and IA/IK were tested using the perforated patch clamp technique. We found that: (1) ISO inhalation evoked a brief tachypnea (∼7s) and that this response disappeared after blocking PCF conduction; (2) the ISO significantly elevated (by 138%) the firing rate of most pulmonary C neurons (17 out of 21) in the nodose ganglion; and (3) ISO perfusion depolarized the pulmonary C neurons in the vitro and inhibited both IA and IK, and this evoked-depolarization was largely diminished after blocking both IA and IK. Our results suggest that ISO is able to stimulate PCFs to elicit tachypnea in rats, at least partly, via inhibiting IA and IK, thereby depolarizing the pulmonary C neurons.
Pathophysiology Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive, SE, Albuquerque, NM 87108, United States.
Zhenxiong
Z
Zhang
Jianguo
J
Zhuang
Cancan
C
Zhang
Fadi
F
Xu
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D051668:Delayed Rectifier Potassium Channels / Q000187:drug effects* / Q000502:physiology; D007530:Isoflurane / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000294:innervation; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D059246:Tachypnea / Q000139:chemically induced
D018685:Anesthetics, Inhalation; D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D007530:Isoflurane