Department of Biological Sciences, Section of Neurobiology, University of Southern California, Los Angeles, CA 90089, USA.
Proc Natl Acad Sci U S A. 2010 Dec 21;107(51):22320-5. doi: 10.1073/pnas.1013664107. Epub 2010 Nov 23.
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.
五种味道已经被确定，每种味道都由一组不同的味觉细胞来传递。其中，与酸刺激相关的酸味是最不被理解的。遗传消融实验已经确定，酸味是由表达 TRP 通道 PKD2L1 和其伴侣 PKD1L3 的一组味觉细胞来检测的，然而，这个细胞亚群检测酸的机制尚不清楚。以前，理解酸味味觉转导的努力受到了阻碍，因为酸味反应细胞只代表味蕾细胞中的一小部分，并且许多对酸味感觉没有作用的离子通道对酸性 pH 值敏感。为了鉴定仅存在于酸味细胞中的酸敏感电导，我们创建了遗传修饰的小鼠，其中酸味细胞通过在 PKD2L1 启动子的控制下表达 YFP 来标记。为了测量对酸味刺激的反应，我们开发了一种方法，其中抽吸电极记录与 NPE-caged 质子的 UV 光解相结合。使用这些方法，我们报告说，对酸味刺激的反应不是由以前认为的 Na(+)通透性通道介导的，而是由 PKD2L1 表达的味觉细胞特有的质子电导介导的。这种电导足以驱动对酸刺激的动作电位发射，在 PKD2L1 表达的味觉细胞的顶膜中富集，并且不受 PKD1L3 基因靶向缺失的影响。我们得出结论，在酸味转导过程中，质子通过顶端质子电导进入，直接去极化味觉细胞膜。
