ArticleGastroenterology2009
Deletion of TRPC4 and TRPC6 in mice impairs smooth muscle contraction and intestinal motility in vivo.
Article in Gastroenterology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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Who cites it
109 citing papers in PubMed, 197 citations in OpenAlex.
- Gut bacteria-derived 5-hydroxyindole is a potent stimulant of intestinal motility via its action on L-type calcium channels.PLoS biology · 2021Trial
- Transient receptor potential canonical (TRPC) channels in diabetes and associated complications.Channels (Austin, Tex.) · 2026Review
- A microbiota-host axis mediates prostaglandin sensitivity: Lactobacillus crispatus as a biomarker and regulator of human labor induction.NPJ biofilms and microbiomes · 2026Article
- Ideal efficacy photoswitching for chromocontrol of TRPC4/5 channel functions in live tissues.Nature chemical biology · 2026Article
- Piezo1 in intestinal smooth muscle cells: Emerging perspectives.The Journal of physiology · 2026Review
- Secretin targets interstitial cells of Cajal to regulate intestinal contractions.EMBO reports · 2025Article
- Non-Ser36 phosphorylated p66Shc inhibits TRPC-dependent and TRPC-independent calcium influx in vascular smooth muscle cells.Biochemical and biophysical research communications · 2025Article
- Smooth muscle cell Piezo1 depletion results in impaired contractile properties in murine small bowel.Communications biology · 2025Article
- Cryo-EM structure of the heteromeric TRPC1/TRPC4 channel.Nature structural & molecular biology · 2025Article
- Lubiprostone Improves Distal Segment-Specific Colonic Contractions through TRPC4 Activation Stimulated by EP3 Prostanoid Receptor.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Biophysical Mechanisms of Vaginal Smooth Muscle Contraction: The Role of the Membrane Potential and Ion Channels.Pathophysiology : the official journal of the International Society for Pathophysiology · 2024Review
- Pharmacological Activation of TRPC6 Channel Prevents Colitis Progression.International journal of molecular sciences · 2024Article
- Direct modulation of TRPC ion channels by Gα proteins.Frontiers in physiology · 2024Review
- A Putative Role for TRPC6 in Immune-Mediated Kidney Injury.International journal of molecular sciences · 2023Review
- Molecular architecture of the GαNature communications · 2023Article
- Negative self-regulation of transient receptor potential canonical 4 by the specific interaction with phospholipase C-δ1.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2023Article
- General anaesthesia-related complications of gut motility with a focus on cholinergic mechanisms, TRP channels and visceral pain.Frontiers in physiology · 2023Article
- Mechanosensing in the Physiology and Pathology of the Gastrointestinal Tract.International journal of molecular sciences · 2022Review
- Relationship Between Intestinal Slow-waves, Spike-bursts, and Motility, as Defined Through High-resolution Electrical and Video Mapping.Journal of neurogastroenterology and motility · 2022Article
- Inhibition of TRPC4 channel activity in colonic myocytes by tricyclic antidepressants disrupts colonic motility causing constipation.Journal of cellular and molecular medicine · 2022Article
49 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsDownstream effects of muscarinic receptor stimulation in intestinal smooth muscle include contraction and intestinal transit. We thought to determine whether classic transient receptor potential (TRPC) channels integrate the intracellular signaling cascades evoked by the stimulated receptors and thereby contribute to the control of the membrane potential, Ca-influx, and cell responses.
methodsWe created trpc4-, trpc6-, and trpc4/trpc6-gene-deficient mice and analyzed them for intestinal smooth muscle function in vitro and in vivo.
resultsIn intestinal smooth muscle cells TRPC4 forms a 55 pS cation channel and underlies more than 80% of the muscarinic receptor-induced cation current (mI(CAT)). The residual mI(CAT) depends on the expression of TRPC6, indicating that TRPC6 and TRPC4 determine mI(CAT) channel activity independent of other channel subunits. In TRPC4-deficient ileal myocytes the carbachol-induced membrane depolarizations are diminished greatly and the atropine-sensitive contraction elicited by acetylcholine release from excitatory motor neurons is reduced greatly. Additional deletion of TRPC6 aggravates these effects. Intestinal transit is slowed down in mice lacking TRPC4 and TRPC6.
conclusionsIn intestinal smooth muscle cells TRPC4 and TRPC6 channels are gated by muscarinic receptors and are responsible for mI(CAT). They couple muscarinic receptors to depolarization of intestinal smooth muscle cells and voltage-activated Ca(2+)-influx and contraction, and thereby accelerate small intestinal motility in vivo.
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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.