Publication Date:
2015-06-13
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kumar, Natasha N -- Velic, Ana -- Soliz, Jorge -- Shi, Yingtang -- Li, Keyong -- Wang, Sheng -- Weaver, Janelle L -- Sen, Josh -- Abbott, Stephen B G -- Lazarenko, Roman M -- Ludwig, Marie-Gabrielle -- Perez-Reyes, Edward -- Mohebbi, Nilufar -- Bettoni, Carla -- Gassmann, Max -- Suply, Thomas -- Seuwen, Klaus -- Guyenet, Patrice G -- Wagner, Carsten A -- Bayliss, Douglas A -- HL074011/HL/NHLBI NIH HHS/ -- HL108609/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):1255-60. doi: 10.1126/science.aaa0922. Epub 2015 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA. ; Institute of Physiology, University of Zurich, Zurich, CH-8057, Switzerland. ; Institute of Veterinary Physiology, University of Zurich, Zurich, CH-8057, Switzerland. Centre de Recherche du CHU de Quebec, Departement de Pediatrie, Faculte de Medecine, Universite Laval, Quebec, QC, Canada. ; Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA. Department of Physiology, Hebei Medical University, Shijiazhuang, Hebei, 050017, China. ; Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA. School of Medical Sciences, University of New South Wales, New South Wales 2052, Australia. Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA. ; Novartis Institutes for Biomedical Research, Basel, CH-4002, Switzerland. ; Institute of Veterinary Physiology, University of Zurich, Zurich, CH-8057, Switzerland. ; Institute of Physiology, University of Zurich, Zurich, CH-8057, Switzerland. Wagnerca@access.uzh.ch bayliss@virginia.edu. ; Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA. Wagnerca@access.uzh.ch bayliss@virginia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068853" target="_blank"〉PubMed〈/a〉
Keywords:
Acidosis, Respiratory/genetics/physiopathology
;
Animals
;
Carbon Dioxide/*physiology
;
Female
;
Gene Deletion
;
Male
;
Mice
;
Mice, Inbred BALB C
;
Mice, Inbred C57BL
;
Mice, Mutant Strains
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Neurons/metabolism/physiology
;
Potassium Channels, Tandem Pore Domain/genetics/*physiology
;
Receptors, G-Protein-Coupled/antagonists & inhibitors/genetics/*physiology
;
*Respiration
;
Trapezoid Body/cytology/metabolism/*physiology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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