title: Molecular underpinnings of ventral surface chemoreceptor function: focus on KCNQ channels.
abstract: Central chemoreception is the mechanism by which CO₂/H(+) -sensitive neurons (i.e. chemoreceptors) regulate breathing in response to changes in tissue CO₂/H(+) . Neurons in the retrotrapezoid nucleus (RTN) directly regulate breathing in response to changes in tissue CO₂/H(+) and function as a key locus of respiratory control by integrating information from several respiratory centres, including the medullary raphe. Therefore, chemosensitive RTN neurons appear to be critically important for maintaining breathing, thus understanding molecular mechanisms that regulate RTN chemoreceptor function may identify therapeutic targets for the treatment of respiratory control disorders. We have recently shown that KCNQ (Kv7) channels in the RTN are essential determinants of spontaneous activity ex vivo, and downstream effectors for serotonergic modulation of breathing. Considering that loss of function mutations in KCNQ channels can cause certain types of epilepsy including those associated with sudden unexplained death in epilepsy (SUDEP), we propose that dysfunctions of KCNQ channels may be one cause for epilepsy and respiratory problems associated with SUDEP. In this review, we will summarize the role of KCNQ channels in the regulation of RTN chemoreceptor function, and suggest that these channels represent useful therapeutic targets for the treatment of respiratory control disorders.
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, 06269, USA.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Mulkey
authors.forename: Virginia E
authors.initials: VE
authors.lastname: Hawkins
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Hawryluk
authors.forename: Ana C
authors.initials: AC
authors.lastname: Takakura
authors.forename: Thiago S
authors.initials: TS
authors.lastname: Moreira
authors.forename: Anastasios V
authors.initials: AV
authors.lastname: Tzingounis
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D002628:Chemoreceptor Cells / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D051656:KCNQ Potassium Channels / Q000235:genetics / Q000378:metabolism*; D012119:Respiration
chemical_list: D051656:KCNQ Potassium Channels