ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2009
Sodium channel mutation in irritable bowel syndrome: evidence for an ion channelopathy.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 2 of them syntheses that pooled it.
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Who cites it
78 citing papers in PubMed, 2 syntheses or guidelines pooled it, 133 citations in OpenAlex.
- The SCN5A Gene Is a Predictor of Phenotype Severity in Brugada Syndrome: A Comprehensive Literature Review.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2023Pooled it
- Evidence-based clinical practice guidelines for irritable bowel syndrome.Journal of gastroenterology · 2015Guideline
- Late IMedicinal research reviews · 2026Review
- Investigating the role of the I-II linker in Nav1.5 channel function.The Journal of general physiology · 2025Article
- Daily sodium intake and constipation in US adult males: an uncommon negative association revealed by national health and nutrition examination survey data from the United States (2005-2010).BMC gastroenterology · 2025Article
- Therapeutic effects of Poncirus fructus on colonic dysfunction and visceral pain in a zymosan-induced irritable bowel syndrome mouse model through interstitial cells of Cajal and ion channel modulation.Frontiers in pharmacology · 2025Article
- Impact of SCN10A Polymorphism on Abdominal Pain Perception and Visceral Hypoalgesia in Crohn's Disease and Ulcerative Colitis.Clinical and translational gastroenterology · 2024Article
- The Role of Ion Channels in Functional Gastrointestinal Disorders (FGID): Evidence of Channelopathies and Potential Avenues for Future Research and Therapeutic Targets.International journal of molecular sciences · 2023Review
- Review
- Systematic review and meta-analysis of calculating degree of comorbidity of irritable bowel syndrome with migraine.BioPsychoSocial medicine · 2023Article
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- Article
- Capsaicin as an amphipathic modulator of NaChannels (Austin, Tex.) · 2022Article
- Digital Therapeutics Care Utilizing Genetic and Gut Microbiome Signals for the Management of Functional Gastrointestinal Disorders: Results From a Preliminary Retrospective Study.Frontiers in microbiology · 2022Article
- Gastrointestinal Symptoms and Channelopathy-Associated Epilepsy.The Journal of pediatrics · 2021Article
- Tetrodotoxin: A New Strategy to Treat Visceral Pain?Toxins · 2021Review
- Frequency of Irritable Bowel Syndrome in Patients with Brugada Syndrome and Drug-Induced Type 1 Brugada Pattern.The American journal of cardiology · 2021Article
- Current applications of mathematical models of the interstitial cells of Cajal in the gastrointestinal tract.WIREs mechanisms of disease · 2021Review
- Evidence-based clinical practice guidelines for irritable bowel syndrome 2020.Journal of gastroenterology · 2021Article
- Structural basis of cytoplasmic NaV1.5 and NaV1.4 regulation.The Journal of general physiology · 2021Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The SCN5A-encoded Na(v)1.5 Na(+) channel is expressed in interstitial cells of Cajal and smooth muscle in the circular layer of the human intestine. Patients with mutations in SCN5A are more likely to report gastrointestinal symptoms, especially abdominal pain. Twin and family studies of irritable bowel syndrome (IBS) suggest a genetic basis for IBS, but no genes have been identified to date. Therefore, our aims were to evaluate SCN5A as a candidate gene involved in the pathogenesis of IBS and to determine physiological consequences of identified mutations. Mutational analysis was performed on genomic DNA obtained from 49 subjects diagnosed with IBS who reported at least moderately severe abdominal pain. One patient hosted a loss-of-function missense mutation, G298S, that was not observed in >3,000 reference alleles derived from 1,500 healthy control subjects. Na(+) currents were recorded from the four common human SCN5A transcripts in transfected HEK-293 cells. Comparing Na(v)1.5 with G298S-SCN5A versus wild type in HEK cells, Na(+) current density was significantly less by 49-77%, and channel activation time was delayed in backgrounds that also contained the common H558R polymorphism. Single-channel measurements showed no change in Na(v)1.5 conductance. Mechanosensitivity was reduced in the H558/Q1077del transcript but not in the other three backgrounds. In conclusion, the G298S-SCN5A missense mutation caused a marked reduction of whole cell Na(+) current and loss of function of Na(v)1.5, suggesting SCN5A as a candidate gene in the pathophysiology of IBS.
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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.