ArticleJournal of neurophysiology2015
HCN channels contribute to serotonergic modulation of ventral surface chemosensitive neurons and respiratory activity.
Article in Journal of neurophysiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 49 citations in OpenAlex.
- Intrinsic pH chemosensitivity of acutely dissociated medullary serotonergic and retrotrapezoid neurones.The Journal of physiology · 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
- 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
- Phox2b-expressing neurons contribute to breathing problems in Kcnq2 loss- and gain-of-function encephalopathy models.Nature communications · 2023Article
- Modulating Hyperpolarization-Activated Cation Currents through Small Molecule Perturbations: Magnitude and Gating Control.Biomedicines · 2023Review
- Criteria for central respiratory chemoreceptors: experimental evidence supporting current candidate cell groups.Frontiers in physiology · 2023Review
- Excitatory and inhibitory effects of HCN channel modulation on excitability of layer V pyramidal cells.PLoS computational biology · 2022Article
- Histamine/H1 receptor signaling in the parafacial region increases activity of chemosensitive neurons and respiratory activity in rats.Journal of neurophysiology · 2022Article
- 5-HT7 receptors expressed in the mouse parafacial region are not required for respiratory chemosensitivity.The Journal of physiology · 2022Article
- Regulation of HCN Channels by Protein Interactions.Frontiers in physiology · 2022Review
- The retrotrapezoid nucleus and the neuromodulation of breathing.Journal of neurophysiology · 2021Review
- TRPM4 mediates a subthreshold membrane potential oscillation in respiratory chemoreceptor neurons that drives pacemaker firing and breathing.Cell reports · 2021Article
- BRAFV600E expression in neural progenitors results in a hyperexcitable phenotype in neocortical pyramidal neurons.Journal of neurophysiology · 2020Article
- Take a deep breath and wake up: The protean role of serotonin preventing sudden death in infancy.Experimental neurology · 2020Review
- High Efficacy by GAL-021: A Known Intravenous Peripheral Chemoreceptor Modulator that Suppresses BKBiomolecules · 2020Article
- Research Advances on Therapeutic Approaches to Congenital Central Hypoventilation Syndrome (CCHS).Frontiers in neuroscience · 2020Review
- Chemosensitivity of Phox2b-expressing retrotrapezoid neurons is mediated in part by input from 5-HT neurons.The Journal of physiology · 2019Article
- Lethal avian influenza A (H5N1) virus replicates in pontomedullary chemosensitive neurons and depresses hypercapnic ventilatory response in mice.American journal of physiology. Lung cellular and molecular physiology · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Chemosensitive neurons in the retrotrapezoid nucleus (RTN) provide a CO2/H(+)-dependent drive to breathe and function as an integration center for the respiratory network, including serotonergic raphe neurons. We recently showed that serotonergic modulation of RTN chemoreceptors involved inhibition of KCNQ channels and activation of an unknown inward current. Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels are the molecular correlate of the hyperpolarization-activated inward current (Ih) and have a high propensity for modulation by serotonin. To investigate whether HCN channels contribute to basal activity and serotonergic modulation of RTN chemoreceptors, we characterize resting activity and the effects of serotonin on RTN chemoreceptors in vitro and on respiratory activity of anesthetized rats in the presence or absence of blockers of KCNQ (XE991) and/or HCN (ZD7288, Cs(+)) channels. We found in vivo that bilateral RTN injections of ZD7288 increased respiratory activity and in vitro HCN channel blockade increased activity of RTN chemoreceptors under control conditions, but this was blunted by KCNQ channel inhibition. Furthermore, in vivo unilateral RTN injection of XE991 plus ZD7288 eliminated the serotonin response, and in vitro serotonin sensitivity was eliminated by application of XE991 and ZD7288 or SQ22536 (adenylate cyclase blocker). Serotonin-mediated activation of RTN chemoreceptors was blocked by a 5-HT7-receptor blocker and mimicked by a 5-HT7-receptor agonist. In addition, serotonin caused a depolarizing shift in the voltage-dependent activation of Ih. These results suggest that HCN channels contribute to resting chemoreceptor activity and that serotonin activates RTN chemoreceptors and breathing in part by a 5-HT7 receptor-dependent mechanism and downstream activation of Ih.
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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.