title: Astrocyte chemoreceptors: mechanisms of H+ sensing by astrocytes in the retrotrapezoid nucleus and their possible contribution to respiratory drive.
abstract: Central chemoreception is the mechanism by which CO(2)/pH-sensitive neurons (i.e. chemoreceptors) regulate breathing, presumably in response to changes in tissue pH. A region of the brainstem called the retrotrapezoid nucleus (RTN) is thought to be an important site of chemoreception; select neurons (i.e. chemoreceptors) in this region sense changes in CO(2)/H(+) and send excitatory glutamatergic drive to respiratory centres to modulate the depth and frequency of breathing. Purinergic signalling may also contribute to chemoreception; for instance, it was shown in vivo that CO(2)/H(+) facilitates ATP release within the RTN to stimulate breathing, and recent evidence suggests that CO(2)/H(+)-sensitive RTN astrocytes are the source of this purinergic drive to breathe. In this review, we summarize evidence that RTN astrocytes sense changes in CO(2)/H(+), identify mechanisms that are likely to confer CO(2)/H(+) sensitivity to RTN astrocytes, including inhibition of heteromeric Kir4.1-Kir5.1 channels and activation of a depolarizing inward current generated by the sodium bicarbonate cotransporter, and discuss the extent to which astrocytes contribute to respiratory drive.
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, 75 North Eagleville Road, Unit 3156, Storrs, CT 06269, USA. daniel.mulkey@uconn.edu
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Mulkey
authors.forename: Ian C
authors.initials: IC
authors.lastname: Wenker
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D002245:Carbon Dioxide / Q000502:physiology; D002628:Chemoreceptor Cells / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D012125:Respiratory Center / Q000502:physiology*; D015656:Respiratory Mechanics / Q000502:physiology*
chemical_list: D002245:Carbon Dioxide