In:
Science, American Association for the Advancement of Science (AAAS), Vol. 348, No. 6240 ( 2015-06-12), p. 1255-1260
Abstract:
Blood gas and tissue pH regulation depend on the ability of the brain to sense CO 2 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 CO 2 -stimulated breathing. Genetic deletion of GPR4 disrupted acidosis-dependent activation of RTN neurons, increased apnea frequency, and blunted ventilatory responses to CO 2 . Reintroduction of GPR4 into RTN neurons restored CO 2 -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 CO 2 . The data identify GPR4 and TASK-2 as distinct, parallel, and essential central mediators of respiratory chemosensitivity.
Type of Medium:
Online Resource
ISSN:
0036-8075
,
1095-9203
DOI:
10.1126/science.aaa0922
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2015
detail.hit.zdb_id:
128410-1
detail.hit.zdb_id:
2066996-3
detail.hit.zdb_id:
2060783-0
SSG:
11