The transduction channel TRPM5 is gated by intracellular calcium in taste cells
The transduction channel TRPM5 is gated by intracellular calcium in taste cells
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DOI：
10.1523/jneurosci.4973-06.2007
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发表时间：
2007-05-23
影响因子：
5.3
通讯作者：
Liman, Emily
中科院分区：
文献类型：
--
作者：
Zhang, Zheng;Zhao, Zhen;Liman, Emily
苦味、甜味和鲜味促味剂通过G蛋白偶联受体检测，G蛋白偶联受体通过共同的第二信使级联反应发出信号，该级联反应涉及味蛋白、磷脂酶C β 2和瞬时受体电位M5（TRPM5）离子通道。磷酸肌醇信号激活TRPM5的机制已经在异源细胞类型中研究，结果相互矛盾。为了解决这个问题并了解TRPM 5在味觉信号传导中的作用，我们利用TRPM 5启动子驱动绿色荧光蛋白表达的小鼠和携带TRPM 5基因靶向缺失的小鼠来明确鉴定味觉受体细胞中的TRPM 5依赖性电流。我们的研究结果表明，细胞内三磷酸肌醇或Ca2+的短暂升高足以在完整的味觉细胞中门控TRPM5依赖性电流，但只有细胞内Ca2+能够激活TRPM5依赖性电流在切除的补丁。在切除的补丁的详细研究表明，TRPM5形成了一个非选择性的阳离子通道，是半激活的8 μ M的Ca2+和脱敏反应，长期暴露于细胞内Ca2+。除了TRPM5基因编码的通道外，我们发现味觉细胞具有第二种类型的Ca2+激活的非选择性阳离子通道，其对细胞内Ca2+不太敏感。这些数据限制了味觉转导的模型，并表明味觉细胞中受体信号传导和膜电位之间的联系。
Bitter, sweet, and umami tastants are detected by G-protein-coupled receptors that signal through a common second-messenger cascade involving gustducin, phospholipase C beta 2, 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 mu M 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.