Heat activation of TRPM5 underlies thermal sensitivity of sweet taste
Heat activation of TRPM5 underlies thermal sensitivity of sweet taste
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DOI：
10.1038/nature04248
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发表时间：
2005-12-15
期刊：
影响因子：
64.8
通讯作者：
Nilius, B
中科院分区：
文献类型：
--
作者：
Talavera, K;Yasumatsu, K;Nilius, B
TRPM5 是 TRP 超家族的一种阳离子通道，在舌头味蕾中高度表达，在甜味、鲜味和苦味的感知中发挥着关键作用(1,2)。 TRPM5 的激活发生在 G 蛋白偶联味觉受体激活的下游，并且被认为会在味觉受体细胞中产生去极化电位 (2)。因此，调节 TRPM5 活性的因素预计会影响味道。在这里，我们表明 TRPM5 是一个对温度高度敏感的热激活通道：在 15 至 35 摄氏度之间，内向 TRPM5 电流急剧增加。TRPM4 是 TRPM5 的密切同源物，显示出类似的温度敏感性。热激活是由于激活曲线随温度变化而产生的，类似于其他热敏 TRP 通道 (3)。此外，我们发现，在野生型小鼠中，将温度升高到 15 至 35 摄氏度会显着增强味觉神经对甜味化合物的反应，但在 Trpm5 敲除小鼠中则不然。 TRPM5 的强烈温度敏感性可能是已知的温度对人类味觉影响的基础 (4-6)，包括高温下甜味感知增强和“热味”，即在没有促味剂的情况下，舌头的加热或冷却会引起味觉的现象 (7)。
TRPM5, a cation channel of the TRP superfamily, is highly expressed in taste buds of the tongue, where it has a key role in the perception of sweet, umami and bitter tastes(1,2). Activation of TRPM5 occurs downstream of the activation of G-protein-coupled taste receptors and is proposed to generate a depolarizing potential in the taste receptor cells(2). Factors that modulate TRPM5 activity are therefore expected to influence taste. Here we show that TRPM5 is a highly temperature-sensitive, heat-activated channel: inward TRPM5 currents increase steeply at temperatures between 15 and 35 degrees C. TRPM4, a close homologue of TRPM5, shows similar temperature sensitivity. Heat activation is due to a temperature-dependent shift of the activation curve, in analogy to other thermosensitive TRP channels(3). Moreover, we show that increasing temperature between 15 and 35 degrees C markedly enhances the gustatory nerve response to sweet compounds in wild-type but not in Trpm5 knockout mice. The strong temperature sensitivity of TRPM5 may underlie known effects of temperature on perceived taste in humans(4-6), including enhanced sweetness perception at high temperatures and 'thermal taste', the phenomenon whereby heating or cooling of the tongue evoke sensations of taste in the absence of tastants(7).