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.
Highlights
Excessive salt intake has become a critical health problem worldwide [1]
Tmc4 was expressed in taste bud cells of the posterior tongue Previous work indicated that high-concentration of salt are expected to be received in the circumvallate papillae (CvP), which is innervated by the glossopharyngeal nerve [7, 9,10,11]
The current observed is not affected by the bath application of NMDG-Cl, no alternative for sodium chloride (NaCl), or amiloride, but is significantly reduced by the anion channel inhibitor, 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB)
Summary
Excessive salt intake has become a critical health problem worldwide [1]. Since saltiness is a basic taste that determines food quality, it is difficult to reduce the salt content in food, and there is no alternative for sodium chloride (NaCl). Prior to reducing salt intake, it is important to understand the mechanism underlying the perception of the “salty taste”. Saltiness is evoked when both sodium and chloride ions are present in the oral cavity. Potassium chloride (KCl) and sodium sulphate (Na2SO4) have a. NaCl-like taste; it is far from the “authentic salt taste”. NaCl has a standard salty taste [2,3,4], which is currently the focus of public attention from sensory and nutritional points of view
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