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KCNQ channels regulate activity of chemosensitive neurons in the retrotrapezoid nucleus
Author(s) -
Hawryluk Joanna Monica,
Wenker Ian C,
Takakura Ana C,
Moreira Thiago S,
Tzingounis Anastasios V,
Mulkey Daniel K
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.1214.10
Subject(s) - serotonergic , neuromodulation , neuroscience , serotonin , premovement neuronal activity , apamin , raphe , chemistry , brainstem , potassium channel , biology , pharmacology , medicine , endocrinology , stimulation , receptor
Chemosensitive neurons in the retrotrapezoid nucleus (RTN) regulate breathing in response to CO2/H+. Their activity is also sensitive to neuromodulatory inputs from other respiratory centers, thus serve as a nexus of respiratory control. However, the molecular mechanisms that control their activity and propensity to neuromodulation are unknown. Here we show in vitro and in vivo that KCNQ channels are critical determinants of RTN neural activity. In brainstem slices isolated from rat pups (P7–12), application of XE991 (selective KCNQ channel blocker) increased basal activity by 1.4 ± 0.2 Hz and decreased serotonin responsiveness by ~50%. While inhibition of SK channels with apamin had no effect on basal activity or serotonin‐sensitivity. Unexpectedly, neither XE991 nor apamin had any effect on other raphe transmitters. We show that blocking KCNQ channels in the RTN in vivo blunts the ventilatory response to serotonin in awake and anesthetized animals. Together, these results indicate that KCNQ channels: i) regulate tonic activity and serotoninergic modulation of RTN neurons in vitro ; ii) are effectors of serotonin modulation of RTN in vivo ; iii) and contribute to respiratory drive in anesthetized and awake animals. Given that 5‐HT dysfunction may contribute to respiratory failure, our findings suggest a new therapeutic avenue for respiratory complications associated with multiple neurological disorders.