Journal
JOURNAL OF PHYSIOLOGICAL SCIENCES
Volume 71, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12576-021-00807-z
Keywords
Salty taste; Transmembrane channel-like protein; Chloride channel; Taste receptor; Taste signaling
Categories
Funding
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [16H03045, 26660108, JP17gm0510016, 17H01962, 18K19728, 26242007, 15K12334, 25242012]
- Core Research for Evolutional Science and Technology (CREST)
- Japan Science and Technology Agency [JPMJTR194F]
- Program for Cross-ministerial Strategic Innovation Promotion Program (SIP) Technologies for creating next-generation agriculture, forestry and fisheries
- Grants-in-Aid for Scientific Research [25242012, 15K12334, 18K19728, 26660108, 16H03045, 17H01962, 26242007] Funding Source: KAKEN
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The study reveals that TMC4 acts as a chloride channel responding to high-concentration NaCl in the oral cavity, facilitating the permeation of organic anions and showing a weaker glossopharyngeal nerve response in Tmc4-deficient mice compared to wild-type littermates.
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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