ArticleNature communications2016
The molecular basis of the genesis of basal tone in internal anal sphincter.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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Who cites it
16 citing papers in PubMed, 35 citations in OpenAlex.
- TMEM16A in gastrointestinal and vascular smooth muscle contractility.The Journal of physiology · 2025Review
- 3D spheroids versus 2D-cultured human adipose stem cells to generate smooth muscle cells in an internal anal sphincter-targeting cryoinjured mouse model.Stem cell research & therapy · 2024Article
- Gallbladder dysfunction caused by MYPT1 ablation triggers cholestasis-induced hepatic fibrosis in mice.Hepatology communications · 2024Article
- TMEM16A in smooth muscle cells acts as a pacemaker channel in the internal anal sphincter.Communications biology · 2024Article
- Differentiation of Adipose-Derived Stem Cells into Smooth Muscle Cells in an Internal Anal Sphincter-Targeting Anal Incontinence Rat Model.Journal of clinical medicine · 2023Article
- Article
- Anoctamin 1 controls bone resorption by coupling ClNature communications · 2022Article
- Article
- Oscillating calcium signals in smooth muscle cells underlie the persistent basal tone of internal anal sphincter.Journal of cellular physiology · 2021Article
- A paradoxical increase of force development in saphenous and tail arteries from heterozygous ANO1 knockout mice.Physiological reports · 2020Article
- Biological Interfaces, Modulation, and Sensing with Inorganic Nano-Bioelectronic Materials.Small methods · 2020Article
- Effects of new-generation TMEM16A inhibitors on calcium-activated chloride currents in rabbit urethral interstitial cells of Cajal.Pflugers Archiv : European journal of physiology · 2017Article
- Is the muscular tone of the internal anal sphincter a property of the syncytium?The Journal of physiology · 2017Article
- ANO1 in intramuscular interstitial cells of Cajal plays a key role in the generation of slow waves and tone in the internal anal sphincter.The Journal of physiology · 2017Article
- Conditional genetic deletion of Ano1 in interstitial cells of Cajal impairs CaAmerican journal of physiology. Gastrointestinal and liver physiology · 2017Article
- Ca2+/calmodulin/MLCK pathway initiates, and RhoA/ROCK maintains, the internal anal sphincter smooth muscle tone.American journal of physiology. Gastrointestinal and liver physiology · 2017Article
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
Abstract
Smooth muscle sphincters exhibit basal tone and control passage of contents through organs such as the gastrointestinal tract; loss of this tone leads to disorders such as faecal incontinence. However, the molecular mechanisms underlying this tone remain unknown. Here, we show that deletion of myosin light-chain kinases (MLCK) in the smooth muscle cells from internal anal sphincter (IAS-SMCs) abolishes basal tone, impairing defecation. Pharmacological regulation of ryanodine receptors (RyRs), L-type voltage-dependent Ca(2+) channels (VDCCs) or TMEM16A Ca(2+)-activated Cl(-) channels significantly changes global cytosolic Ca(2+) concentration ([Ca(2+)]i) and the tone. TMEM16A deletion in IAS-SMCs abolishes the effects of modulators for TMEM16A or VDCCs on a RyR-mediated rise in global [Ca(2+)]i and impairs the tone and defecation. Hence, MLCK activation in IAS-SMCs caused by a global rise in [Ca(2+)]i via a RyR-TMEM16A-VDCC signalling module sets the basal tone. Targeting this module may lead to new treatments for diseases like faecal incontinence.
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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.