ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2015
Ranolazine inhibits voltage-gated mechanosensitive sodium channels in human colon circular smooth muscle cells.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Late IMedicinal research reviews · 2026Review
- Investigating the role of the I-II linker in Nav1.5 channel function.The Journal of general physiology · 2025Article
- Mechanosensing Piezo channels in gastrointestinal disorders.The Journal of clinical investigation · 2023Review
- Bioelectric regulation of intestinal stem cells.Trends in cell biology · 2023Review
- Review
- The gut microbiome and hypertension.Nature reviews. Nephrology · 2023Review
- Single coronary artery presenting dilated cardiomyopathy and hyperlipidemia with theFrontiers in cardiovascular medicine · 2023Review
- Tracking Gut Motility in Organ and Cultures.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Mechanosensing in the Physiology and Pathology of the Gastrointestinal Tract.International journal of molecular sciences · 2022Review
- Capsaicin as an amphipathic modulator of NaChannels (Austin, Tex.) · 2022Article
- Gut feelings: mechanosensing in the gastrointestinal tract.Nature reviews. Gastroenterology & hepatology · 2022Review
- The role of mechanosensitive ion channels in the gastrointestinal tract.Frontiers in physiology · 2022Review
- Mechanotransduction at the Plasma Membrane-Cytoskeleton Interface.International journal of molecular sciences · 2021Review
- Gastrointestinal Symptoms and Channelopathy-Associated Epilepsy.The Journal of pediatrics · 2021Article
- Mechanotransduction in gastrointestinal smooth muscle cells: role of mechanosensitive ion channels.American journal of physiology. Gastrointestinal and liver physiology · 2021Review
- Lubeluzole: from anti-ischemic drug to preclinical antidiarrheal studies.Pharmacological reports : PR · 2021Article
- Article
- Article
- Irritable bowel syndrome patients have SCN5A channelopathies that lead to decreased NaAmerican journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Voltage-gated sodium channels: (NaThe Journal of physiology · 2018Review
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Human jejunum smooth muscle cells (SMCs) and interstitial cells of Cajal (ICCs) express the SCN5A-encoded voltage-gated, mechanosensitive sodium channel NaV1.5. NaV1.5 contributes to small bowel excitability, and NaV1.5 inhibitor ranolazine produces constipation by an unknown mechanism. We aimed to determine the presence and molecular identity of Na(+) current in the human colon smooth muscle and to examine the effects of ranolazine on Na(+) current, mechanosensitivity, and smooth muscle contractility. Inward currents were recorded by whole cell voltage clamp from freshly dissociated human colon SMCs at rest and with shear stress. SCN5A mRNA and NaV1.5 protein were examined by RT-PCR and Western blots, respectively. Ascending human colon strip contractility was examined in a muscle bath preparation. SCN5A mRNA and NaV1.5 protein were identified in human colon circular muscle. Freshly dissociated human colon SMCs had Na(+) currents (-1.36 ± 0.36 pA/pF), shear stress increased Na(+) peaks by 17.8 ± 1.8% and accelerated the time to peak activation by 0.7 ± 0.3 ms. Ranolazine (50 μM) blocked peak Na(+) current by 43.2 ± 9.3% and inhibited shear sensitivity by 25.2 ± 3.2%. In human ascending colon strips, ranolazine decreased resting tension (31%), reduced the frequency of spontaneous events (68%), and decreased the response to smooth muscle electrical field stimulation (61%). In conclusion, SCN5A-encoded NaV1.5 is found in human colonic circular smooth muscle. Ranolazine blocks both peak amplitude and mechanosensitivity of Na(+) current in human colon SMCs and decreases contractility of human colon muscle strips. Our data provide a likely mechanistic explanation for constipation induced by ranolazine.
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