A proton current drives action potentials in genetically identified sour taste cells
A proton current drives action potentials in genetically identified sour taste cells
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DOI：
10.1073/pnas.1013664107
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发表时间：
2010-12-21
影响因子：
11.1
通讯作者：
Liman, Emily R.
中科院分区：
文献类型：
--
作者：
Chang, Rui B.;Waters, Hang;Liman, Emily R.
已经鉴定了五种味道，每种味道都由一组单独的味觉细胞转导。在这些酸中，与酸刺激有关的酸是最不了解的。基因消融实验已经确定，酸是由表达TRP通道PKD2L1及其伴侣PKD1L3的味觉细胞亚群检测到的，然而，该亚群细胞检测酸的机制仍不清楚。以前的努力，以了解酸味转导已受阻，因为酸反应细胞只代表一小部分的细胞在味蕾，和许多离子通道，没有在酸传感的作用是敏感的酸性pH值。为了确定酸敏感电导独特的酸细胞，我们创建了转基因小鼠，其中酸细胞标记的表达YFP的PKD2L1启动子的控制下。为了测量对酸刺激的反应，我们开发了一种方法，其中吸力电极记录与NPE笼状质子的UV光解相结合。使用这些方法，我们报告说，酸刺激的反应是不介导的Na+渗透通道，如以前所认为的，而是介导的质子传导特异性PKD2L1表达的味觉细胞。这种电导足以驱动响应于酸刺激的动作电位放电，在表达PKD2L1的味觉细胞的顶膜中富集，并且不受PKD1L3基因的靶向缺失的影响。我们的结论是，在酸的转导，质子进入通过顶端质子传导直接去质子化的味觉细胞膜。
Five tastes have been identified, each of which is transduced by a separate set of taste cells. Of these sour, which is associated with acid stimuli, is the least understood. Genetic ablation experiments have established that sour is detected by a subset of taste cells that express the TRP channel PKD2L1 and its partner PKD1L3, however the mechanisms by which this subset of cells detects acids remain unclear. Previous efforts to understand sour taste transduction have been hindered because sour responsive cells represent only a small fraction of cells in a taste bud, and numerous ion channels with no role in sour sensing are sensitive to acidic pH. To identify acid-sensitive conductances unique to sour cells, we created genetically modified mice in which sour cells were marked by expression of YFP under the control of the PKD2L1 promoter. To measure responses to sour stimuli we developed a method in which suction electrode recording is combined with UV photolysis of NPE-caged proton. Using these methods, we report that responses to sour stimuli are not mediated by Na+ permeable channels as previously thought, but instead are mediated by a proton conductance specific to PKD2L1-expressing taste cells. This conductance is sufficient to drive action potential firing in response to acid stimuli, is enriched in the apical membrane of PKD2L1-expressing taste cells and is not affected by targeted deletion of the PKD1L3 gene. We conclude that, during sour transduction, protons enter through an apical proton conductance to directly depolarize the taste cell membrane.