Electrophysiological basis of sour taste transduction

描述(由申请人提供)：大多数脊椎动物物种对五种基本口味做出反应：甜、苦、鲜味、酸和咸，每一种都提供关于所摄取食物的营养含量和安全性的独特信息。五种味觉品质中的每一种都是由舌头和上颌上皮味蕾中的味觉感受器细胞的不同亚群来检测的。虽然在了解调节苦味、甜味和鲜味的分子和机制方面取得了很大进展，但对酸味的电生理学基础知之甚少。检测酸味的细胞可以通过Trp离子通道PKD2L1的表达来识别，而PKD2L1本身并不是酸味所必需的。在最近的工作中，我们使用了一只由PKD2L1启动子驱动黄色荧光蛋白(YFP)的小鼠，我们证明了酸味细胞具有以前没有特征的质子电导，该质子电导位于顶部，并携带内向电流响应细胞外酸化。这导致我们提出了一个模型，在该模型中，质子通过质子通道进入细胞，使细胞去极化，从而导致动作电位和递质释放。此外，质子进入可能引起胞浆酸化，这可能作用于静息K+通道，进一步使细胞去极化。这一过程可能在多个步骤中受到调节，使系统能够适应生物体不同的条件和需求。目前的建议包括三个具体目标，利用这些新产生的转基因小鼠系和转录组分析的最新结果来测试这一模型，并进一步阐明酸味转导的机制。味觉是人类和其他生物调节其摄食行为的重要方式，因此，味觉信号机制的识别可以直接影响人类的健康和福祉。

DESCRIPTION (provided by applicant): Most vertebrate species are responsive to five basic tastes: sweet, bitter, umami, sour and salty, each of which provides unique information on the nutritional content and safety of ingested food. Each of the five taste qualities is detected by a distinct subset of taste receptor cells found in taste buds on the tongue and the palate epithelium. While great strides have been made in understanding the molecules and mechanisms that mediate bitter, sweet, and umami tastes, relatively little is known about the electrophysiological basis for sour taste. The cells that detect sour taste can be identified by expression of the TRP ion channel PKD2L1, which itself is not necessary for sour taste. In recent work, using a mouse in which yellow fluorescent protein (YFP) was driven by the promoter of Pkd2l1, we showed that sour taste cells have a previously uncharacterized proton conductance which is apically located and carries an inward current in response to extracellular acidification. This has led us to propose a model in which proton entry through the proton channel depolarizes the cells leading to action potentials and transmitter release. In addition, proton entry may cause cytosolic acidification, which could act on resting K+ channels to further depolarize the cells. This process may be subject to modulation at multiple steps, allowing the system to adapt to varying conditions and needs of the organism. The present proposal include three specific aims that take advantage of these newly generated transgenic mouse lines and recent results from transcriptome profiling to test this model and to further elucidate mechanisms of sour transduction. Taste is an essential way in which humans and other organisms regulate their ingestive behavior and the identification of mechanisms of taste signaling can therefore have a direct impact on human health and well-being.