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Effects of isoflurane on dopaminergic neurotransmission (659.8)
Author(s) -
Bonvicino Christina,
Baumgart Joel,
Zhou Zhenyu,
Hemmings Hugh
Publication year - 2014
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.28.1_supplement.659.8
Subject(s) - ventral tegmental area , neuroscience , dopaminergic , substantia nigra , neurotransmission , isoflurane , pars compacta , exocytosis , dopamine , chemistry , inhibitory postsynaptic potential , kainate receptor , glutamate receptor , ampa receptor , biology , receptor , secretion , biochemistry , organic chemistry
Volatile anesthetics have poorly understood mechanisms of action, despite their wide usage in medicine. Current knowledge of the molecular and cellular mechanisms of anesthetic action is insufficient to explain amnesia, unconsciousness or immobilization, the principal features of general anesthesia. The volatile anesthetic isoflurane alters synaptic transmission by blocking ionotropic glutamate receptors postsynaptically and/or by enhancing fast inhibitory transmission and tonic currents mediated by GABA A receptors. However, dopaminergic neurons, which are primarily found in the ventral tegmental area and the substantia nigra pars compacta, play roles in cognition, attention, voluntary movement, among other functions, pose another potential site of anesthetic action. Here we test the hypothesis that isoflurane perturbs the stimulus‐secretion coupling between [Ca 2+ ] i and exocytosis in dopaminergic neurons by probing synaptic vesicle exocytosis and nerve terminal [Ca 2+ ] i . Laser‐ scanning fluorescence image measurements of [Ca 2+ ] i in neonatal rat dopaminergic neurons were made using the cell permeant calcium indicator Fluo‐5N and action potential‐evoked exocytosis was measured with vesicular monoamine transporter‐ pHluorin (vMAT‐pH). The effects of isoflurane on [Ca 2+ ] i and exocytosis at varying external [Ca 2+ ] reveal a change in the Ca 2+ sensitivity of exocytosis. These data suggest that isoflurane inhibits dopamine release from synaptic vesicles by shifting the coupling between [Ca 2+ ] i and exocytosis.