{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:03:55Z","timestamp":1791266635454,"version":"4.1.0"},"reference-count":51,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,12,9]]},"abstract":"<jats:p>\n                    The transduction of taste is a fundamental process that allows animals to discriminate nutritious from noxious substances. Three taste modalities, bitter, sweet, and amino acid, are mediated by G protein-coupled receptors that signal through a common transduction cascade: activation of phospholipase C \u03b22, leading to a breakdown of phosphatidylinositol-4,5-bisphosphate (PIP\n                    <jats:sub>2<\/jats:sub>\n                    ) into diacylglycerol and inositol 1,4,5-trisphosphate, which causes release of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    from intracellular stores. The ion channel, TRPM5, is an essential component of this cascade; however, the mechanism by which it is activated is not known. Here we show that heterologously expressed TRPM5 forms a cation channel that is directly activated by micromolar concentrations of intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    (\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>1\/2<\/jats:sub>\n                    = 21 \u03bcM). Sustained exposure to Ca\n                    <jats:sup>2+<\/jats:sup>\n                    desensitizes TRPM5 channels, but PIP\n                    <jats:sub>2<\/jats:sub>\n                    reverses desensitization, partially restoring channel activity. Whole-cell TRPM5 currents can be activated by intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and show strong outward rectification because of voltage-sensitive gating of the channels. TRPM5 channels are nonselective among monovalent cations and not detectably permeable to divalent cations. We propose that the regulation of TRPM5 by Ca\n                    <jats:sup>2+<\/jats:sup>\n                    mediates sensory activation in the taste system.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2334159100","type":"journal-article","created":{"date-parts":[[2003,12,9]],"date-time":"2003-12-09T13:17:48Z","timestamp":1070975868000},"page":"15160-15165","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":389,"title":["Intracellular Ca\n                    <sup>2+<\/sup>\n                    and the phospholipid PIP\n                    <sub>2<\/sub>\n                    regulate the taste transduction ion channel TRPM5"],"prefix":"10.1073","volume":"100","author":[{"given":"Dan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Biological Sciences and Program in Neuroscience, University of Southern California, Los Angeles, CA 90089"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily R.","family":"Liman","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Program in Neuroscience, University of Southern California, Los Angeles, CA 90089"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2003,12]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/35093002"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.10.5791"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1069259"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.082127599"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/39807"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature719"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00652-9"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4160(03)00063-0"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-21-08259.1997"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5461.2229"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00448-3"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1998.5549"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/35079100"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1062473"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00719-5"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/35079092"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1058519"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb781"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn952"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00071-0"},{"key":"e_1_3_2_21_2","first-page":"1","volume":"277","year":"2002","unstructured":"Margolskee, R. 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