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HCN channels contribute to serotonergic modulation of chemoreceptors in the retrotrapezoid nucleus
Author(s) -
Hawkins Virginia,
Hawryluk Joanna,
Takakura Ana,
Williams Donny,
Moreira Thaigo,
Tzingounis Anastasios,
Mulkey Daniel
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.1214.11
Subject(s) - serotonergic , neuroscience , serotonin , chemistry , neuromodulation , biology , central nervous system , receptor , biochemistry
Chemosensitive neurons in the retrotrapezoid nucleus (RTN) provide a CO2‐dependent drive to breathe, and function as a key locus of respiratory control by integrating information from several respiratory centers including the medullary raphe. Recent evidence showed that mechanisms underlying serotonergic modulation of RTN neurons involves inhibition of KCNQ channels and activation of an unknown inward current. Evidence also shows that RTN neurons produce a hyperpolarization‐activated inward current (Ih) at negative potentials. HCN channels are the molecular correlate of Ih and have a high propensity for neuromodulation. Therefore, we hypothesize that HCN channels contribute to serotonergic modulation of RTN neurons. We investigated this in vitro and in vivo using selective blockers for KCNQ (XE991) and HCN (ZD7288) channels. Membrane potential recordings in rat brain slices show that serotonin application increased chemoreceptor activity by ~1 Hz. Consistent with our previous evidence, XE991 decreased serotonin‐responsiveness by ~50%. The residual serotonin‐sensitivity in XE991 was blocked by ZD7288. In anesthetized rats RTN injection of XE991 blunted serotonin‐responsiveness and together XE991 and ZD7288 completely eliminated the respiratory response to serotonin. These results indicate that HCN channels contribute to serotonergic modulation of RTN chemoreceptors and respiratory drive. Funding sources: CURE Epilepsy Foundation (AVT, DKM), NIH HL104101 (DKM), NS073981 (AVT), and the Sao Paulo Research Foundation (FAPESP) (ACT, TSM).