ArticleScience (New York, N.Y.)2015
PHYSIOLOGY. Regulation of breathing by CO₂ requires the proton-activated receptor GPR4 in retrotrapezoid nucleus neurons.
Article in Science (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed, 231 citations in OpenAlex.
- Circuit Mechanisms Underlying the Contribution of Leptin Receptor-Expressing Neurons in the Nucleus Tractus Solitarius to Ventilatory Homeostasis.Neuroscience bulletin · 2026Article
- Quantification of ventilatory control in sleep apnea: from physiological insight to computable loop gain.Sleep · 2026Review
- Intrinsic pH chemosensitivity of acutely dissociated medullary serotonergic and retrotrapezoid neurones.The Journal of physiology · 2026Article
- Loss of proton-sensing TDAG8 increases tumor progression in mouse models of colon cancer.Molecular oncology · 2026Article
- GABAergic Inhibition from the Nucleus Tractus Solitarius to Ventrolateral Medulla Phox2b Neurons Modulates Central Respiratory Chemoreflex and Ventilatory Homeostasis.Neuroscience bulletin · 2026Article
- Sex Differences in the Effects of Etonogestrel on Respiratory Recovery in an In Vivo Rat Model of Central Chemoreflex Impairment.Acta physiologica (Oxford, England) · 2026Article
- Tachykinergic signaling mediated by NK1 receptors in the respiratory parafacial region drives respiratory output and contributes to the chemoreflex response to COPflugers Archiv : European journal of physiology · 2026Article
- Review
- Sensing molecular carbon dioxide: a translational focus for respiratory disease.Physiological reviews · 2025Review
- Oxytocinergic signalling in the respiratory parafacial region increases the activity of chemosensitive neurons and respiratory output.The Journal of physiology · 2025Article
- Retrotrapezoid nucleus chemoreception: mechanisms of function and contributions to disordered breathing in disease.Trends in neurosciences · 2025Review
- Cell Settling, Migration, and Stochastic Cancer Gene Expression Suggest Potassium Membrane Flux May Initiate pH Reversal.Biomolecules · 2025Article
- Structural basis of stepwise proton sensing-mediated GPCR activation.Cell research · 2025Article
- Homeostatic regulation of a motor circuit through temperature sensing rather than activity sensing.Current biology : CB · 2025Article
- A Molecularly Defined Medullary Network for Control of Respiratory Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Intrinsic responses to hypoxia and hypercapnia of neurons in the cardiorespiratory center of the ventral medulla of newborn rats.Pflugers Archiv : European journal of physiology · 2025Article
- Neuroanatomical and neurochemical organization of brainstem and forebrain circuits involved in breathing regulation.Journal of neurophysiology · 2025Review
- Sudden Unexpected Death in Epilepsy: Central Respiratory Chemoreception.International journal of molecular sciences · 2025Review
- Article
- Interactions between Arousal State and COThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
80 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 5 institutions in 4 countries.
Funding
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.