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Acute Intermittent Hypoxia Increases Synaptic Inhibition in the Respiratory Network in the Presence of Norepinephrine. An In Vitro Study in Mice
Author(s) -
Elsen Frank,
Zanella Sebastien,
Doi Atsushi,
Garcia Alfredo,
Ramirez Jan Marino
Publication year - 2011
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.25.1_supplement.1074.4
Subject(s) - hypoxia (environmental) , norepinephrine , in vitro , chemistry , respiratory system , intermittent hypoxia , neuroscience , anesthesia , pharmacology , medicine , biology , dopamine , oxygen , biochemistry , organic chemistry , obstructive sleep apnea
Repeated periods of central hypoxia occur in sleep apneas and Rett syndrome. In these disorders, an imbalance of bioamines has been described. We hypothesize that the effect of a neuromodulator (norepinephrine (NE)) on the respiratory network can be altered by acute intermittent hypoxia (AIH). We exposed brainstem slices (P6–10 mice) to AIH with or without NE and we recorded the fictive respiratory activity generated in the preBötzinger complex (preBötC). Under control conditions, NE regularizes the respiratory rhythm. Following AIH respiratory activity is slightly unstable but becomes highly irregular if slices are exposed to NE at the same time. Using whole cell recordings, we measured excitatory and inhibitory postsynaptic currents (EPSCs, IPSCs) of inspiratory neurons in the preBötC. After AIH, the IPSCs amplitude and frequency increased, whereas no significant changes in EPSCs were observed. In the presence of NE, AIH induces an even larger increase of IPSC amplitudes, whereas the frequency of EPSCs tended to decrease. Co‐application of strychnine (STR, glycine‐R antagonist) during AIH + NE prevented the instability. However, application of STR after AIH + NE did not restore a normal rhythm. We suggest that the AIH induced change in the responsiveness to NE has potentially important clinical implications and may convey state‐dependency to various breathing disorders. Supported by NIH.