Detection of NaCl and KCl in TRPV1 knockout mice
Detection of NaCl and KCl in TRPV1 knockout mice
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DOI：
10.1093/chemse/bjl024
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发表时间：
2006-11-01
期刊：
影响因子：
3.5
通讯作者：
Kinnamon, Sue
中科院分区：
文献类型：
--
作者：
Ruiz, Collin;Gutknecht, Stephanie;Kinnamon, Sue
阿米洛利敏感和不敏感机制都有助于 NaCl 味觉转导。阿米洛利敏感机制依赖于上皮Na+通道ENaC，该通道广泛表达于蕈状味觉细胞的顶膜上。阿米洛利不敏感机制在周味蕾和叶味蕾中占主导地位，最近据报道涉及非选择性阳离子通道 TRPV1 的变体。我们使用 TRPV1 敲除小鼠和野生型 (C57BL/6J) 对照进行 2 瓶偏好和阈值实验，以测试存在和不存在阿米洛利的情况下的 NaCl 偏好和检测阈值。令人惊讶的是，TRPV1 敲除小鼠不仅在阿米洛利存在的情况下检测到 NaCl，而且在野生型小鼠避免的浓度下，它们更喜欢 NaCl 而不是水。两种基因型的 NaCl 检测阈值均在 2 至 3 mM 之间。阿米洛利提高了野生型小鼠的检测阈值，但没有提高敲除小鼠的检测阈值。与野生型对照相比，基因敲除小鼠也更喜欢 100 mM KCl，这表明 TRPV1 受体可能介导对盐的普遍厌恶反应。对消耗数据的分析还表明，与野生型小鼠相比，TRPV1 敲除小鼠摄入了更多的 NaCl（无论是否含有阿米洛利）和 KCl 溶液。然而，偏好比和消耗量的比较表明，野生型和TRPV1敲除小鼠都以非常相似的方式避免柠檬酸，这表明TRPV1受体不介导柠檬酸的检测。这些数据综合起来表明，一定有其他机制导致阿米洛利不敏感的 NaCl 反应。
Both amiloride-sensitive and -insensitive mechanisms contribute to NaCl taste transduction. The amiloride-sensitive mechanism relies on the epithelial Na+ channel ENaC, which is widely expressed on the apical membrane of fungiform taste cells. The amiloride-insensitive mechanism, which predominates in circumvallate and foliate taste buds, was recently reported to involve a variant of the nonselective cation channel TRPV1. We performed 2-bottle preference and threshold experiments with TRPV1 knockout mice and wild-type (C57BL/6J) controls to test for NaCl preference and detection thresholds in the presence and absence of amiloride. Surprisingly, TRPV1 knockout mice not only detected NaCl in the presence of amiloride but they preferred NaCl over water at concentrations avoided by the wild-type mice. NaCl detection thresholds were between 2 and 3 mM for both genotypes. Amiloride increased the detection thresholds of wild-type mice but not knockout mice. The knockout mice also preferred 100 mM KCl compared with wild-type controls, suggesting that TRPV1 receptors may mediate a general aversive response to salts. Analyses of consumption data also revealed that TRPV1 knockout mice ingested more of the NaCl, with and without amiloride, and KCl solutions than the wild-type mice. However, comparisons of preference ratios and consumption volumes indicated that both wild-type and TRPV1 knockout mice avoided citric acid in quite a similar manner, suggesting that TRPV1 receptors do not mediate the detection of citric acid. These data, taken together, suggest that additional mechanisms must contribute to the amiloride-insensitive NaCl response.