Isoflurane depresses the response of inspiratory hypoglossal motoneurons to serotonin in vivo.
BACKGROUND
Endogenous serotonin (5-HT) provides important excitatory drive to inspiratory hypoglossal motoneurons (IHMNs). In vitro studies show that activation of postsynaptic 5-HT receptors decreases a leak K+ channel conductance and depolarizes hypoglossal motoneurons (HMNs). In contrast, volatile anesthetics increase this leak K+ channel conductance, which causes neuronal membrane hyperpolarization and depresses HMN excitability. Clinical studies show upper airway obstruction, indicating HMN depression, even at subanesthetic concentrations. The authors hypothesized that if anesthetic activation of leak K+ channels caused neuronal depression in vivo, this effect could be antagonized with serotonin. In this case, the neuronal response to picoejected serotonin would be greater during isoflurane than with no isoflurane.


METHODS
Studies were performed in decerebrate, vagotomized, paralyzed, and mechanically ventilated dogs during hypercapnic hyperoxia. The authors studied the effect of approximately 0.3 minimum alveolar concentration (MAC) isoflurane on the spontaneous discharge frequency patterns of single IHMNs and on the neuronal response to picoejection of 5-HT.


RESULTS
Normalized data (mean +/- SD, n = 19) confirmed that 0.3 +/- 0.1 MAC isoflurane markedly reduced the spontaneous peak discharge frequency by 48 +/- 19% (P < 0.001) and depressed the slope of the spontaneous discharge patterns. The increase in neuronal frequency in response to 5-HT was reduced by 34 +/- 22% by isoflurane (P < 0.001).


CONCLUSIONS
Subanesthetic concentrations of isoflurane strongly depressed canine IHMNs in vivo. The neuronal response to 5-HT was also depressed by isoflurane, suggesting that anesthetic activation of leak K+ channels, which is expected to result in a larger 5-HT response, was not a dominant mechanism in this depression.
Brandes
Ivo F
IF
Department of Anesthesiology, Medical College of Wisconsin, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, USA.
Zuperku
Edward J
EJ
Stucke
Astrid G
AG
Hopp
Francis A
FA
Jakovcevic
Danica
D
Stuth
Eckehard A E
EA
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D007002:Hypoglossal Nerve / Q000187:drug effects* / Q000502:physiology; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*
D018685:Anesthetics, Inhalation; D015221:Potassium Channels; D011963:Receptors, GABA-A; D012701:Serotonin; D007530:Isoflurane