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The Journal of Neuroscience, May 23, 2007, 27(21):5777-5786; doi:10.1523/JNEUROSCI.4973-06.2007

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Cellular/Molecular
The Transduction Channel TRPM5 Is Gated by Intracellular Calcium in Taste Cells

Zheng Zhang,¹ Zhen Zhao,¹ Robert Margolskee,² and Emily Liman¹

¹Department of Biological Sciences and Program in Neuroscience, University of Southern California, Los Angeles, California 90089, and ²Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029

Correspondence should be addressed to Emily R. Liman, Program in Neurosciences, University of Southern California, 3641 Watt Way, Los Angeles, CA 90089. Email: liman{at}usc.edu

Bitter, sweet, and umami tastants are detected by G-protein-coupled receptors that signal through a common second-messenger cascade involving gustducin, phospholipase C ß2, 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 µM 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.

Key words: transient receptor potential; bitter; sweet; inositol trisphosphate; ion channel; calcium

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Received Nov. 15, 2006; revised April 18, 2007; accepted April 19, 2007.

Correspondence should be addressed to Emily R. Liman, Program in Neurosciences, University of Southern California, 3641 Watt Way, Los Angeles, CA 90089. Email: liman{at}usc.edu

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