ArticlePLoS biology2019
Trpm4 ion channels in pre-Bötzinger complex interneurons are essential for breathing motor pattern but not rhythm.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 58 citations in OpenAlex.
- Comparative Ion Channel Transcriptomes of NK1R and Somatostatin Neurons in the PreBötzinger Complex of the Ventrolateral Medulla.Molecular neurobiology · 2026Article
- Comparative Ion Channel Transcriptomes of NK1R and Somatostatin Neurons in the preBötzinger Complex of the Ventrolateral Medulla.Research square · 2026Article
- Preventive and therapeutic effects of magnesium sulfate on nikethamide-induced seizures: Implications for COVID-19 treatment.World journal of methodology · 2025Article
- Review
- The TRP channels serving as chemical-to-electrical signal converter.Physiological reviews · 2025Review
- Neuroanatomical and neurochemical organization of brainstem and forebrain circuits involved in breathing regulation.Journal of neurophysiology · 2025Review
- Interdependence of cellular and network properties in respiratory rhythm generation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Inspiratory and sigh breathing rhythms depend on distinct cellular signalling mechanisms in the preBötzinger complex.The Journal of physiology · 2024Article
- Cholinergic stimulation stabilizes TRPM4 in the plasma membrane of cortical pyramidal neurons.Frontiers in cell and developmental biology · 2024Article
- Article
- Interdependence of cellular and network properties in respiratory rhythmogenesis.bioRxiv : the preprint server for biology · 2023Article
- Role of NaCell reports · 2023Article
- Article
- TRPM4 regulates hilar mossy cell loss in temporal lobe epilepsy.BMC biology · 2023Article
- Synchronization of inspiratory burst onset along the ventral respiratory column in the neonate mouse is mediated by electrotonic coupling.BMC biology · 2023Article
- Predictions and experimental tests of a new biophysical model of the mammalian respiratory oscillator.eLife · 2022Article
- Inspiratory rhythm generation is stabilized byJournal of neurophysiology · 2022Article
- Dynamics of ramping bursts in a respiratory neuron model.Journal of computational neuroscience · 2022Article
- A glibenclamide-sensitive TRPM4-mediated component of CA1 excitatory postsynaptic potentials appears in experimental autoimmune encephalomyelitis.Scientific reports · 2022Article
- Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Inspiratory breathing movements depend on pre-Bötzinger complex (preBötC) interneurons that express calcium (Ca2+)-activated nonselective cationic current (ICAN) to generate robust neural bursts. Hypothesized to be rhythmogenic, reducing ICAN is predicted to slow down or stop breathing; its contributions to motor pattern would be reflected in the magnitude of movements (output). We tested the role(s) of ICAN using reverse genetic techniques to diminish its putative ion channels Trpm4 or Trpc3 in preBötC neurons in vivo. Adult mice transduced with Trpm4-targeted short hairpin RNA (shRNA) progressively decreased the tidal volume of breaths yet surprisingly increased breathing frequency, often followed by gasping and fatal respiratory failure. Mice transduced with Trpc3-targeted shRNA survived with no changes in breathing. Patch-clamp and field recordings from the preBötC in mouse slices also showed an increase in the frequency and a decrease in the magnitude of preBötC neural bursts in the presence of Trpm4 antagonist 9-phenanthrol, whereas the Trpc3 antagonist pyrazole-3 (pyr-3) showed inconsistent effects on magnitude and no effect on frequency. These data suggest that Trpm4 mediates ICAN, whose influence on frequency contradicts a direct role in rhythm generation. We conclude that Trpm4-mediated ICAN is indispensable for motor output but not the rhythmogenic core mechanism of the breathing central pattern generator.
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