Clues to understanding cold sensation: Thermodynamics and electrophysiological analysis of the cold receptor TRPM8
Clues to understanding cold sensation: Thermodynamics and electrophysiological analysis of the cold receptor TRPM8
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DOI：
10.1073/pnas.0406773101
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发表时间：
2004-10-26
影响因子：
11.1
通讯作者：
Latorre, R
中科院分区：
文献类型：
--
作者：
Brauchi, S;Orio, P;Latorre, R
冷和薄荷醇受体TRPM 8，也称为CMR 1，是兴奋性离子通道的瞬时受体电位（TRP）家族的成员。TRPM 8是一个由低温、电压和薄荷醇激活的通道。在这项研究中，我们的特点是冷和电压诱导的激活TRPM 8通道，试图确定参与通道激活的温度和电压依赖性组件。在平衡条件下，降低温度有两种效果。(i)它使归一化电导与电压曲线沿电压轴沿着向左移动。这种效应表明，当通道处于开放构型时，有序度较高。(ii)它增加了最大通道开放概率，表明温度影响电压依赖性和非依赖性途径。在18 ℃和25 ℃之间的温度范围内，伴随着活化过程的焓（Δ H = -112千卡/摩尔）和熵（Δ S = -384千卡/摩尔K）的大变化。在相同温度范围内计算的Q（10）为24。这种热力学分析强烈表明，开放的过程涉及大的通道形成蛋白的构象变化。因此，开放和封闭配置之间的高度依赖于温度的转变是可能的，因为焓和熵都很大，并相互补偿。我们的数据还表明，温度和电压相互作用，以增强通道开放变构。
The cold and menthol receptor, TRPM8, also designated CMR1, is a member of the transient receptor potential (TRP) family of excitatory ion channels. TRPM8 is a channel activated by cold temperatures, voltage, and menthol. In this study, we characterize the cold and voltage-induced activation of TRPM8 channel in an attempt to identify the temperature- and voltage-dependent components involved in channel activation. Under equilibrium conditions, decreasing temperature has two effects. (i) It shifts the normalized conductance vs. voltage curves toward the left, along the voltage axis. This effect indicates that the degree of order is higher when the channel is in the open configuration. (ii) It increases the maximum channel open probability, suggesting that temperature affects both voltage-dependent and -independent pathways. in the temperature range between 18degreesC and 25degreesC, large changes in enthalpy (DeltaH = -112 kcal/mol) and entropy (DeltaS = -384 cal/mol K) accompany the activation process. The Q(10) calculated in the same temperature range is 24. This thermodynamic analysis strongly suggests that the process of opening involves large conformational changes of the channel-forming protein. Therefore, the highly temperature-dependent transition between open and closed configurations is possible because enthalpy and entropy are both large and compensate each other. Our data also demonstrate that temperature and voltage interact allosterically to enhance channel opening.