| First Author | Kumar NN | Year | 2015 |
| Journal | Science | Volume | 348 |
| Issue | 6240 | Pages | 1255-60 |
| PubMed ID | 26068853 | Mgi Jnum | J:224758 |
| Mgi Id | MGI:5689041 | Doi | 10.1126/science.aaa0922 |
| Citation | Kumar NN, et al. (2015) PHYSIOLOGY. Regulation of breathing by CO(2) requires the proton-activated receptor GPR4 in retrotrapezoid nucleus neurons. Science 348(6240):1255-60 |
| abstractText | 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. |
