PHYSIOLOGY. Regulation of breathing by CO₂ requires the proton-activated receptor GPR4 in retrotrapezoid nucleus neurons.

TitlePHYSIOLOGY. Regulation of breathing by CO₂ requires the proton-activated receptor GPR4 in retrotrapezoid nucleus neurons.
Publication TypeJournal Article
Year of Publication2015
AuteursKumar, NN, Velic, A, Soliz, J, Shi, Y, Li, K, Wang, S, Weaver, JL, Sen, J, Abbott, SBG, Lazarenko, RM, Ludwig, M-G, Perez-Reyes, E, Mohebbi, N, Bettoni, C, Gassmann, M, Suply, T, Seuwen, K, Guyenet, PG, Wagner, CA, Bayliss, DA
JournalScience
Volume348
Issue6240
Pagination1255-60
Date Published2015 Jun 12
ISSN1095-9203
KeywordsAcidosis, Respiratory, Animals, Carbon Dioxide, Female, Gene Deletion, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Mutant Strains, Neurons, Potassium Channels, Tandem Pore Domain, Receptors, G-Protein-Coupled, Respiration, Trapezoid Body
Abstract

Blood gas and tissue pH regulation depend on the ability of the brain to sense CO2 and/or H(+) and alter breathing appropriately, a homeostatic process called central respiratory chemosensitivity. We show that selective expression of the proton-activated receptor GPR4 in chemosensory neurons of the mouse retrotrapezoid nucleus (RTN) is required for CO2-stimulated breathing. Genetic deletion of GPR4 disrupted acidosis-dependent activation of RTN neurons, increased apnea frequency, and blunted ventilatory responses to CO2. Reintroduction of GPR4 into RTN neurons restored CO2-dependent RTN neuronal activation and rescued the ventilatory phenotype. Additional elimination of TASK-2 (K(2P)5), a pH-sensitive K(+) channel expressed in RTN neurons, essentially abolished the ventilatory response to CO2. The data identify GPR4 and TASK-2 as distinct, parallel, and essential central mediators of respiratory chemosensitivity.

DOI10.1126/science.aaa0922
Alternate JournalScience
PubMed ID26068853
PubMed Central IDPMC5171229
Grant ListR01 HL074011 / HL / NHLBI NIH HHS / United States
T32 GM008136 / GM / NIGMS NIH HHS / United States
R01 HL108609 / HL / NHLBI NIH HHS / United States
HL074011 / HL / NHLBI NIH HHS / United States
HL108609 / HL / NHLBI NIH HHS / United States