Cooling-sensitive TRPM8 is thermostat of skin temperature against cooling.
Cooling-sensitive TRPM8 is thermostat of skin temperature against cooling.
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冷却敏感的TRPM8是皮肤温度的恒温器，而冷却。
DOI：
10.1371/journal.pone.0017504
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发表时间：
2011-03-02
期刊：
影响因子：
3.7
通讯作者：
Kobayashi S
中科院分区：
文献类型：
--
作者：
Tajino K;Hosokawa H;Maegawa S;Matsumura K;Dhaka A;Kobayashi S
我们已经证明，皮肤对降温敏感的受体可以作为皮肤温度的恒温器来对抗降温。然而，恒温器的分子尚不清楚。在这里，我们研究了冷却敏感的TRPM8通道是否作为恒温器。当温度(T)低于阈值28.4°C时，HEK293电池中的TRPM8产生输出(Y)。输出(Y)由两个方程给出：在T&gT；28.4°C，y = 0；在T<；28.4°C，y = -k(T-28.4°C)。这些方程表明，TRPM8是一个定向比较器，可以根据热差的负值(ΔT = T-28.4°C)获得输出(Y)。如果TRPM8在皮肤中的负ΔT依赖输出诱导递归地最小化ΔT而使皮肤变暖的反应，TRPM8起到抵抗降温的恒温器的作用。在TRPM8基因缺陷的小鼠身上，我们探索了TRPM8是否诱导了使皮肤变暖以抵御降温的反应。在行为调节方面，当室温为10°C时，TRPM8诱导行为移至加热的地板(35°C)以温暖鞋底皮肤。在自主神经调节中，TRPM8诱导产热棕色脂肪组织(BAT)抵抗降温的活动。当在中性室温(27℃)下对整个躯干皮肤施加薄荷脑时，TRPM8诱导核心温度升高，使躯干皮肤略有升温。相比之下，当室内温度从27摄氏度降至10摄氏度时，TRPM8导致核心温度略有上升，但由于向周围环境的大量热泄漏，TRPM8缺陷小鼠和野生型小鼠的皮肤温度都严重下降。这表明，TRPM8驱动的吸热系统在保持皮肤温度以抵御降温方面的效果较差。综上所述，我们发现TRPM8是皮肤温度抵抗降温的恒温分子。
We have shown that cutaneous cooling-sensitive receptors can work as thermostats of skin temperature against cooling. However, molecule of the thermostat is not known. Here, we studied whether cooling-sensitive TRPM8 channels act as thermostats. TRPM8 in HEK293 cells generated output (y) when temperature (T) was below threshold of 28.4°C. Output (y) is given by two equations: At T >28.4°C, y = 0; At T <28.4°C, y = -k(T – 28.4°C). These equations show that TRPM8 is directional comparator to elicits output (y) depending on negative value of thermal difference (ΔT = T – 28.4°C). If negative ΔT-dependent output of TRPM8 in the skin induces responses to warm the skin for minimizing ΔT recursively, TRPM8 acts as thermostats against cooling. With TRPM8-deficient mice, we explored whether TRPM8 induces responses to warm the skin against cooling. In behavioral regulation, when room temperature was 10°C, TRPM8 induced behavior to move to heated floor (35°C) for warming the sole skin. In autonomic regulation, TRPM8 induced activities of thermogenic brown adipose tissue (BAT) against cooling. When menthol was applied to the whole trunk skin at neutral room temperature (27°C), TRPM8 induced a rise in core temperature, which warmed the trunk skin slightly. In contrast, when room was cooled from 27 to 10°C, TRPM8 induced a small rise in core temperature, but skin temperature was severely reduced in both TRPM8-deficient and wild-type mice by a large heat leak to the surroundings. This shows that TRPM8-driven endothermic system is less effective for maintenance of skin temperature against cooling. In conclusion, we found that TRPM8 is molecule of thermostat of skin temperature against cooling.
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作者：
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发表时间：
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通讯作者：
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