Magnetic Entropy as a Proposed Gating Mechanism for Magnetogenetic Ion Channels
Magnetic Entropy as a Proposed Gating Mechanism for Magnetogenetic Ion Channels
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DOI：
10.1016/j.bpj.2019.01.003
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发表时间：
2019-02-05
影响因子：
3.4
通讯作者：
Robinson, Jacob T.
中科院分区：
文献类型：
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作者：
Duret, Guillaume;Polali, Sruthi;Robinson, Jacob T.
磁敏感离子通道将使研究人员能够更好地研究特定脑细胞如何影响自由移动动物的行为;然而，最近基于生物铁蛋白纳米颗粒的“磁遗传”离子通道的报道受到质疑，因为已知的生物物理机制无法解释实验观察结果。在这里，我们再现了弱磁介导的钙反应在HEK细胞表达以前发表的TRPV 4-铁蛋白融合蛋白。我们发现，这种磁灵敏度衰减时，我们降低的通道的温度灵敏度，但不是当我们降低的机械灵敏度的通道，这表明该通道的磁灵敏度是热介导的。作为这种热介导的磁响应的潜在机制，我们提出铁蛋白颗粒的磁熵的变化可以通过磁热效应产生热量，从而门相关的温度敏感的离子通道。与其他形式的磁加热不同，磁热机制可以在退磁期间冷却磁性颗粒。为了测试这一预测，我们基于冷敏感TRPM 8通道构建了一个磁致通道。我们观察到冷门控通道的磁响应与磁热假说是一致的。总之，这些新数据和我们提出的作用机制为理解离子通道如何被低频磁场激活提供了额外的资源。
Magnetically sensitive ion channels would allow researchers to better study how specific brain cells affect behavior in freely moving animals; however, recent reports of "magnetogenetic" ion channels based on biogenic ferritin nano-particles have been questioned because known biophysical mechanisms cannot explain experimental observations. Here, we reproduce a weak magnetically mediated calcium response in HEK cells expressing a previously published TRPV4-ferritin fusion protein. We find that this magnetic sensitivity is attenuated when we reduce the temperature sensitivity of the channel but not when we reduce the mechanical sensitivity of the channel, suggesting that the magnetic sensitivity of this channel is thermally mediated. As a potential mechanism for this thermally mediated magnetic response, we propose that changes in the magnetic entropy of the ferritin particle can generate heat via the magnetocaloric effect and consequently gate the associated temperature-sensitive ion channel. Unlike other forms of magnetic heating, the magnetocaloric mechanism can cool magnetic particles during demagnetization. To test this prediction, we constructed a magnetogenetic channel based on the cold-sensitive TRPM8 channel. Our observation of a magnetic response in cold-gated channels is consistent with the magnetocaloric hypothesis. Together, these new data and our proposed mechanism of action provide additional resources for understanding how ion channels could be activated by low-frequency magnetic fields.