Faculty Collaboration Database

Isoflurane depresses the response of inspiratory hypoglossal motoneurons to serotonin in vivo. Anesthesiology 2007 Apr;106(4):736-45

Date

04/07/2007

Pubmed ID

17413911

DOI

10.1097/01.anes.0000264750.93769.99

Scopus ID

2-s2.0-34147182706 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

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).

CONCLUSION: 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.

Author List

Brandes IF, Zuperku EJ, Stucke AG, Hopp FA, Jakovcevic D, Stuth EA

Authors

Astrid G. Stucke MD Professor in the Anesthesiology department at Medical College of Wisconsin
Eckehard A. Stuth MD Professor in the Anesthesiology department at Medical College of Wisconsin
Edward J. Zuperku PhD Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Anesthetics, Inhalation
Animals
Dogs
Dose-Response Relationship, Drug
Female
Hypoglossal Nerve
Isoflurane
Male
Motor Neurons
Potassium Channels
Receptors, GABA-A
Serotonin