PubMed 26068853

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNK3 , KCNK5

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

Authors: Natasha N Kumar, Ana Velic, Jorge Soliz, Yingtang Shi, Keyong Li, Sheng Wang, Janelle L Weaver, Josh Sen, Stephen B G Abbott, Roman M Lazarenko, Marie-Gabrielle Ludwig, Edward Perez-Reyes, Nilufar Mohebbi, Carla Bettoni, Max Gassmann, Thomas Suply, Klaus Seuwen, Patrice G Guyenet, Carsten A Wagner, Douglas A Bayliss

Journal, date & volume: Science, 2015 Jun 12 , 348, 1255-60

PubMed link:

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.