Morenilla-Palao Cruz, Luis Enoch, Fernández-Peña Carlos, Quintero Eva, Weaver Janelle L, Bayliss Douglas A, Viana Félix
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, 03550 San Juan de Alicante, Spain.
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, 03550 San Juan de Alicante, Spain.
Cell Rep. 2014 Sep 11;8(5):1571-82. doi: 10.1016/j.celrep.2014.08.003. Epub 2014 Sep 4.
Animals sense cold ambient temperatures through the activation of peripheral thermoreceptors that express TRPM8, a cold- and menthol-activated ion channel. These receptors can discriminate a very wide range of temperatures from innocuous to noxious. The molecular mechanism responsible for the variable sensitivity of individual cold receptors to temperature is unclear. To address this question, we performed a detailed ion channel expression analysis of cold-sensitive neurons, combining bacterial artificial chromosome (BAC) transgenesis with a molecular-profiling approach in fluorescence-activated cell sorting (FACS)-purified TRPM8 neurons. We found that TASK-3 leak potassium channels are highly enriched in a subpopulation of these sensory neurons. The thermal threshold of TRPM8 cold neurons is decreased during TASK-3 blockade and in mice lacking TASK-3, and, most importantly, these mice display hypersensitivity to cold. Our results demonstrate a role of TASK-3 channels in thermosensation, showing that a channel-based combinatorial strategy in TRPM8 cold thermoreceptors leads to molecular specialization and functional diversity.
动物通过激活表达TRPM8（一种冷和薄荷醇激活的离子通道）的外周温度感受器来感知寒冷的环境温度。这些感受器能够区分从无害到有害的非常广泛的温度范围。单个冷感受器对温度的可变敏感性的分子机制尚不清楚。为了解决这个问题，我们结合细菌人工染色体（BAC）转基因技术和荧光激活细胞分选（FACS）纯化的TRPM8神经元中的分子分析方法，对冷敏感神经元进行了详细的离子通道表达分析。我们发现TASK-3渗漏钾通道在这些感觉神经元的一个亚群中高度富集。在TASK-3阻断期间以及在缺乏TASK-3的小鼠中，TRPM8冷神经元的热阈值降低，并且，最重要的是，这些小鼠表现出对寒冷的超敏反应。我们的结果证明了TASK-3通道在温度感觉中的作用，表明TRPM8冷感受器中基于通道的组合策略导致分子特化和功能多样性。
