ArticleThe Journal of biological chemistry2010
Tmem16A encodes the Ca2+-activated Cl- channel in mouse submandibular salivary gland acinar cells.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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Who cites it
117 citing papers in PubMed, 199 citations in OpenAlex.
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- WNK kinase is a vasoactive chloride sensor in endothelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- CFTR expression in human salivary gland acinar cells.American journal of physiology. Cell physiology · 2024Article
- Function and Regulation of the Calcium-Activated Chloride Channel Anoctamin 1 (TMEM16A).Handbook of experimental pharmacology · 2024Article
- Structural and functional analysis of salivary intercalated duct cells reveals a secretory phenotype.The Journal of physiology · 2023Article
- The Anion Channel TMEM16a/Ano1 Modulates CFTR Activity, but Does Not Function as an Apical Anion Channel in Colonic Epithelium from Cystic Fibrosis Patients and Healthy Individuals.International journal of molecular sciences · 2023Article
- Major depression-related factor NEGR1 controls salivary secretion in mouse submandibular glands.iScience · 2023Article
- CaCell calcium · 2022Article
- Optimizing Soluble Cues for Salivary Gland Tissue Mimetics Using a Design of Experiments (DoE) Approach.Cells · 2022Article
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- EnterotoxigenicPathogens (Basel, Switzerland) · 2022Review
57 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Activation of an apical Ca(2+)-dependent Cl(-) channel (CaCC) is the rate-limiting step for fluid secretion in many exocrine tissues. Here, we compared the properties of native CaCC in mouse submandibular salivary gland acinar cells to the Ca(2+)-gated Cl(-) currents generated by Tmem16A and Best2, members from two distinct families of Ca(2+)-activated Cl(-) channels found in salivary glands. Heterologous expression of Tmem16A and Best2 transcripts in HEK293 cells produced Ca(2+)-activated Cl(-) currents with time and voltage dependence and inhibitor sensitivity that resembled the Ca(2+)-activated Cl(-) current found in native salivary acinar cells. Best2(-/-) and Tmem16A(-/-) mice were used to further characterize the role of these channels in the exocrine salivary gland. The amplitude and the biophysical footprint of the Ca(2+)-activated Cl(-) current in submandibular gland acinar cells from Best2-deficient mice were the same as in wild type cells. Consistent with this observation, the fluid secretion rate in Best2 null mice was comparable with that in wild type mice. In contrast, submandibular gland acinar cells from Tmem16A(-/-) mice lacked a Ca(2+)-activated Cl(-) current and a Ca(2+)-mobilizing agonist failed to stimulate Cl(-) efflux, requirements for fluid secretion. Furthermore, saliva secretion was abolished by the CaCC inhibitor niflumic acid in wild type and Best2(-/-) mice. Our results demonstrate that both Tmem16A and Best2 generate Ca(2+)-activated Cl(-) current in vitro with similar properties to those expressed in native cells, yet only Tmem16A appears to be a critical component of the acinar Ca(2+)-activated Cl(-) channel complex that is essential for saliva production by the submandibular gland.
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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.