title: The transduction channel TRPM5 is gated by intracellular calcium in taste cells.
abstract: Bitter, sweet, and umami tastants are detected by G-protein-coupled receptors that signal through a common second-messenger cascade involving gustducin, phospholipase C beta2, and the transient receptor potential M5 (TRPM5) ion channel. The mechanism by which phosphoinositide signaling activates TRPM5 has been studied in heterologous cell types with contradictory results. To resolve this issue and understand the role of TRPM5 in taste signaling, we took advantage of mice in which the TRPM5 promoter drives expression of green fluorescent protein and mice that carry a targeted deletion of the TRPM5 gene to unequivocally identify TRPM5-dependent currents in taste receptor cells. Our results show that brief elevation of intracellular inositol trisphosphate or Ca2+ is sufficient to gate TRPM5-dependent currents in intact taste cells, but only intracellular Ca2+ is able to activate TRPM5-dependent currents in excised patches. Detailed study in excised patches showed that TRPM5 forms a nonselective cation channel that is half-activated by 8 microM Ca2+ and that desensitizes in response to prolonged exposure to intracellular Ca2+. In addition to channels encoded by the TRPM5 gene, we found that taste cells have a second type of Ca2+-activated nonselective cation channel that is less sensitive to intracellular Ca2+. These data constrain proposed models for taste transduction and suggest a link between receptor signaling and membrane potential in taste cells.
authors.affiliation: Department of Biological Sciences and Program in Neuroscience, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhao
authors.forename: Robert
authors.initials: R
authors.lastname: Margolskee
authors.forename: Emily
authors.initials: E
authors.lastname: Liman
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism*; D015640:Ion Channel Gating / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D018408:Patch-Clamp Techniques; D015398:Signal Transduction / Q000502:physiology*; D050053:TRPM Cation Channels / Q000096:biosynthesis* / Q000235:genetics; D013650:Taste Buds / Q000378:metabolism*
chemical_list: D050053:TRPM Cation Channels; C498617:Trpm5 protein, mouse; D002118:Calcium