Molecular underpinnings of ventral surface chemoreceptor function: focus on KCNQ channels

• Published in: The Journal of physiology Vol. 593; no. 5; pp. 1075 - 1081
• Main Authors: Mulkey, Daniel K., Hawkins, Virginia E., Hawryluk, Joanna M., Takakura, Ana C., Moreira, Thiago S., Tzingounis, Anastasios V.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-03-2015; BlackWell Publishing Ltd
• Subjects: Animals; Brain Stem - cytology; Brain Stem - metabolism; Brain Stem - physiology; Chemoreceptor Cells - metabolism; Chemoreceptor Cells - physiology; Epilepsy; Humans; KCNQ Potassium Channels - genetics; KCNQ Potassium Channels - metabolism; Medical research; Respiration; Symposium Section Reviews: New Advances in the Neural Control of Breathing
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2014.286500

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.