TMC4 is a novel chloride channel involved in high-concentration salt taste sensation

Yoichi Kasahara; Masataka Narukawa; Yoshiro Ishimaru; Shinji Kanda; Chie Umatani; Yasunori Takayama; Makoto Tominaga; Yoshitaka Oka; Kaori Kondo; Takashi Kondo; Ayako Takeuchi; Takumi Misaka; Keiko Abe; Tomiko Asakura

doi:10.1186/s12576-021-00807-z

TMC4 is a novel chloride channel involved in high-concentration salt taste sensation

J Physiol Sci. 2021 Aug 25;71(1):23. doi: 10.1186/s12576-021-00807-z.

Authors

Yoichi Kasahara^#¹, Masataka Narukawa^#^{1

2}, Yoshiro Ishimaru³, Shinji Kanda⁴, Chie Umatani⁴, Yasunori Takayama⁵, Makoto Tominaga^{5

6}, Yoshitaka Oka⁴, Kaori Kondo⁷, Takashi Kondo⁷, Ayako Takeuchi⁸, Takumi Misaka¹, Keiko Abe^#^{1

9}, Tomiko Asakura^#¹⁰

Affiliations

¹ Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
² Department of Food and Nutrition, Kyoto Women's University, 35 Kitahiyoshicho Imakumano Higashiyama, Kyoto, 605-8501, Japan.
³ Department of Agricultural Chemistry, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki, Kanagawa, 214-8571, Japan.
⁴ Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
⁵ Division of Cell Signaling, National Institute for Physiological Sciences, National Institutes of Natural Sciences, 5-1 Aza-Higashiyama, Myodaijicho, Okazaki, Aichi, 444-8787, Japan.
⁶ Thermal Biology Research Group, Exploratory Research Center On Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, 5-1 Aza-Higashiyama, Myodaijicho, Okazaki, Aichi, 444-8787, Japan.
⁷ Laboratory for Developmental Genetics, RIKEN-IMS, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
⁸ Department of Integrative and Systems Physiology, Faculty of Medical Sciences, and Life Science Innovation Center, University of Fukui, Fukui, 910-1193, Japan.
⁹ Kanagawa Institute of Industrial Science and Technology (KISTEC), LiSE 4F C-4, 3-25-13 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-0821, Japan.
¹⁰ Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan. aka7308@mail.ecc.u-tokyo.ac.jp.

^# Contributed equally.

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.

Keywords: Chloride channel; Salty taste; Taste receptor; Taste signaling; Transmembrane channel-like protein.

MeSH terms

Amiloride
Animals
Chloride Channels / genetics
HEK293 Cells
Humans
Membrane Proteins
Mice
Sodium Chloride*
Taste*

Substances

Chloride Channels
Membrane Proteins
TMC4 protein, human
Sodium Chloride
Amiloride

Grants and funding

JPMJTR194F/adaptable and seamless technology transfer program through target-driven r and d