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Isoflurane stimulates firing frequency and masks chemosensitivity of CO 2 ‐inhibited GABAergic neurons in situ
Author(s) -
Johansen Sara Louise,
Iceman Kimberly E.,
Richerson George B.,
Harris Michael B.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1137.10
Subject(s) - isoflurane , gabaergic , postsynaptic potential , neuroscience , inhibitory postsynaptic potential , chemistry , serotonergic , pharmacology , anesthesia , serotonin , biology , medicine , receptor , biochemistry
Anesthesia mechanisms are poorly understood, despite their importance in clinical medicine and potential to confound experimental results. Postsynaptic effects such as γ‐aminobutyric acid (GABA) inhibition through GABA A receptors are recognized, but presynaptic mechanisms are largely undescribed. We have shown that isoflurane inhibits and masks chemosensitivity of CO 2 ‐stimulated serotonin synthesizing neurons in situ , and we hypothesize this effect is dose‐dependent. We further hypothesize that isoflurane stimulates and masks sensitivity of CO 2 ‐inhibited GABAergic neurons. Before and during isoflurane exposure, in situ raphé extracellular recordings were made during hypercapnia. Juxtacellular labeling and immunohistochemistry identified neuron phenotype. Results show that isoflurane dose‐dependently inhibits serotonergic neurons, increases firing frequency of GABAergic neurons and masks chemosensitivity. Isoflurane‐induced increases in GABAergic neuron firing may contribute to central inhibition characteristic of anesthesia. Prevention of CO 2 ‐sensitive inhibition of GABAergic neurons and postsynaptic disinhibition may contribute to attenuated hypercapnic responses during anesthesia. These conclusions suggest two presynaptic sites of anesthetic action that may be critical to mechanisms of anesthesia. NIH 2U54NS041069–06A1, IAB Fellowship, Alaska INBRE P20GM103395.