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TMC4 is a Novel Chloride Channel Involved in High-concentration Salt Taste Sensation

Overview
Journal J Physiol Sci
Specialty Physiology
Date 2021 Aug 25
PMID 34429071
Citations 11
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Abstract

"Salty taste" sensation is evoked when sodium and chloride ions are present together in the oral cavity. The presence of an epithelial cation channel that receives Na has previously been reported. However, no molecular entity involving Cl receptors has been elucidated. We report the strong expression of transmembrane channel-like 4 (TMC4) in the circumvallate and foliate papillae projected to the glossopharyngeal nerve, mediating a high-concentration of NaCl. Electrophysiological analysis using HEK293T cells revealed that TMC4 was a voltage-dependent Cl channel and the consequent currents were completely inhibited by NPPB, an anion channel blocker. TMC4 allowed permeation of organic anions including gluconate, but their current amplitudes at positive potentials were less than that of Cl. Tmc4-deficient mice showed significantly weaker glossopharyngeal nerve response to high-concentration of NaCl than the wild-type littermates. These results indicated that TMC4 is a novel chloride channel that responds to high-concentration of NaCl.

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References
1.
Cheng Y, Wang K, Geng L, Sun J, Xu W, Liu D . Identification of candidate diagnostic and prognostic biomarkers for pancreatic carcinoma. EBioMedicine. 2019; 40:382-393. PMC: 6412825. DOI: 10.1016/j.ebiom.2019.01.003. View

2.
Liu S, Wang S, Zou L, Li J, Song C, Chen J . TMC1 is an essential component of a leak channel that modulates tonotopy and excitability of auditory hair cells in mice. Elife. 2019; 8. PMC: 6853638. DOI: 10.7554/eLife.47441. View

3.
Dreinhofer J, Gogelein H, Greger R . Blocking kinetics of Cl- channels in colonic carcinoma cells (HT29) as revealed by 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB). Biochim Biophys Acta. 1988; 946(1):135-42. DOI: 10.1016/0005-2736(88)90466-x. View

4.
Nakanishi H, Kurima K, Kawashima Y, Griffith A . Mutations of TMC1 cause deafness by disrupting mechanoelectrical transduction. Auris Nasus Larynx. 2014; 41(5):399-408. PMC: 4176506. DOI: 10.1016/j.anl.2014.04.001. View

5.
Kimura K, Ohtubo Y, Tateno K, Takeuchi K, Kumazawa T, Yoshii K . Cell-type-dependent action potentials and voltage-gated currents in mouse fungiform taste buds. Eur J Neurosci. 2013; 39(1):24-34. DOI: 10.1111/ejn.12388. View