ReviewThe Journal of physiology2016
Proton detection and breathing regulation by the retrotrapezoid nucleus.
Review in The Journal of physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 98 citations in OpenAlex.
- Nocturnal hypercapnia in obstructive sleep apnoea and obesity hypoventilation: from pathophysiology to measurement and treatment.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- A Computational Model of the Respiratory CPG for the Artificial Control of Breathing.Bioengineering (Basel, Switzerland) · 2025Article
- Retrotrapezoid nucleus chemoreception: mechanisms of function and contributions to disordered breathing in disease.Trends in neurosciences · 2025Review
- 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
- Sudden Unexpected Death in Epilepsy: Central Respiratory Chemoreception.International journal of molecular sciences · 2025Review
- Interactions between Arousal State and COThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- The Respiratory Compensation Point: Mechanisms and Relation to the Maximal Metabolic Steady State.Sports medicine (Auckland, N.Z.) · 2024Review
- Intrinsic Molecular Proton Sensitivity Underlies GPR4 Effects on Retrotrapezoid Nucleus Neuronal Activation and COThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Sex andJournal of neurophysiology · 2024Article
- Time-restricted feeding reveals a role for neural respiratory clocks in optimizing daily ventilatory-metabolic coupling in mice.American journal of physiology. Endocrinology and metabolism · 2024Article
- Genetic identification of medullary neurons underlying congenital hypoventilation.Science advances · 2024Article
- Article
- Transformation of Our Understanding of Breathing Control by Molecular Tools.Annual review of physiology · 2023Review
- Criteria for central respiratory chemoreceptors: experimental evidence supporting current candidate cell groups.Frontiers in physiology · 2023Review
- Advances in the Understanding of Two-Pore Domain TASK Potassium Channels and Their Potential as Therapeutic Targets.Molecules (Basel, Switzerland) · 2022Review
- Genetic variants in eleven central and peripheral chemoreceptor genes in sudden infant death syndrome.Pediatric research · 2022Article
- pH and proton-sensitive receptors in brain ischemia.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Medullary astrocytes mediate irregular breathing patterns generation in chronic heart failure through purinergic P2X7 receptor signalling.EBioMedicine · 2022Article
- Article
- Central respiratory chemoreception.Handbook of clinical neurology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
We discuss recent evidence which suggests that the principal central respiratory chemoreceptors are located within the retrotrapezoid nucleus (RTN) and that RTN neurons are directly sensitive to [H(+) ]. RTN neurons are glutamatergic. In vitro, their activation by [H(+) ] requires expression of a proton-activated G protein-coupled receptor (GPR4) and a proton-modulated potassium channel (TASK-2) whose transcripts are undetectable in astrocytes and the rest of the lower brainstem respiratory network. The pH response of RTN neurons is modulated by surrounding astrocytes but genetic deletion of RTN neurons or deletion of both GPR4 and TASK-2 virtually eliminates the central respiratory chemoreflex. Thus, although this reflex is regulated by innumerable brain pathways, it seems to operate predominantly by modulating the discharge rate of RTN neurons, and the activation of RTN neurons by hypercapnia may ultimately derive from their intrinsic pH sensitivity. RTN neurons increase lung ventilation by stimulating multiple aspects of breathing simultaneously. They stimulate breathing about equally during quiet wake and non-rapid eye movement (REM) sleep, and to a lesser degree during REM sleep. The activity of RTN neurons is regulated by inhibitory feedback and by excitatory inputs, notably from the carotid bodies. The latter input operates during normo- or hypercapnia but fails to activate RTN neurons under hypocapnic conditions. RTN inhibition probably limits the degree of hyperventilation produced by hypocapnic hypoxia. RTN neurons are also activated by inputs from serotonergic neurons and hypothalamic neurons. The absence of RTN neurons probably underlies the sleep apnoea and lack of chemoreflex that characterize congenital central hypoventilation syndrome.
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Registered trials
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.