Electrophysiological basis of sour taste transduction

酸味转导的电生理基础

• 批准号: 9246482
• 负责人: EMILY R. LIMAN
• 金额: $ 35.06万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9246482
• 关键词: Acids; Action Potentials; Address; Apical; Cell membrane; Cells; Cytosol; Data; Detection; Electrodes; Electrophysiology (science); Epithelium; Event; Feeding behaviors; Food; Health; Hormones; Human; Ion Channel; Label; Laboratories; Mediating; Membrane; Modeling; Molecular; Mus; Neurons; Neurotransmitter Receptor; Neurotransmitters; Nutritional; Organism; Palate; Physiological; Potassium Channel; Process; Proteins; Protons; Receptor Activation; Receptor Cell; Receptor Signaling; Rest; Safety; Sensory; Sensory Receptors; Signal Pathway; Signal Transduction; Suction; System; Taste Buds; Taste Perception; Testing; Tongue; Transgenic Mice; Work; base; biophysical properties; cell type; experimental study; extracellular; insight; neurotransmitter release; novel; novel strategies; patch clamp; promoter; public health relevance; receptor; response; sweet taste perception; taste transduction; transcriptome; transcriptome sequencing; voltage

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.

描述（由申请人提供）：大多数脊椎动物都对五种基本口味反应：甜，苦，鲜味，酸和咸，每种都提供了有关摄入食物的营养含量和安全性的独特信息。五种味道质量中的每一个都通过在舌头和上皮上皮上的味蕾中发现的明显的味觉受体细胞来检测到。尽管在理解介导苦，甜和鲜味的味道的分子和机制方面取得了长足的进步，但对酸味的电生理基础知之甚少。可以通过表达TRP离子通道PKD2L1来识别检测酸味的细胞，而TRP离子通道PKD2L1本身对于酸味并不是必需的。在最近的工作中，使用PKD2L1的启动子驱动黄色荧光蛋白（YFP）的小鼠，我们表明酸味细胞具有先前未表征的质子电导，该蛋白质是顶端位于顶端的，并且在对细胞外酸化的响应中携带了内向电流。这使我们提出了一个模型，在该模型中，质子通过质子通道的进入将细胞去极化，从而导致动作电位和发射器释放。另外，质子进入可能会导致胞质酸化，这可能作用于静止的K+通道以进一步使细胞去极化。该过程可能会在多个步骤中受到调制，从而使系统适应了生物体的不同条件和需求。目前的建议包括三个特定的目标，这些目标利用了这些新生成的转基因小鼠系，以及转录组分析的最新结果来测试该模型，并进一步阐明了酸转导机制。味道是人类和其他生物体调节其摄入行为的重要方法，因此识别味觉信号的机制可以直接影响人类健康和福祉。