Ultrasound activates mechanosensitive TRAAK K(+) channels through the lipid membrane.
Ultrasound activates mechanosensitive TRAAK K(+) channels through the lipid membrane.
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DOI：
10.1073/pnas.2006980118
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发表时间：
2021-02-09
影响因子：
11.1
通讯作者：
Brohawn SG
中科院分区：
文献类型：
--
作者：
Sorum B;Rietmeijer RA;Gopakumar K;Adesnik H;Brohawn SG
超声波刺激调节可兴奋细胞的电活动，包括大脑和中枢神经系统的神经元。与其他神经调节技术相比，超声具有以下几个优点：例如，它可以通过颅骨无创地传播并集中到大脑深处区域。然而，超声波对神经活动影响的分子基础尚不清楚。在这里，我们表明超声波以类似于典型机械激活的方式通过膜激活机械敏感离子通道 TRAAK，可能是通过增加膜张力来促进通道开放。这些结果表明机械敏感通道是对超声波的生理反应的基础，并且可以作为基因靶向细胞的声神经调节的工具。超声波调节可兴奋细胞的电活动，与其他神经调节技术相比具有优势；例如，它可以通过颅骨无创地传播并集中到大脑深处区域。然而，超声神经调节的基本细胞、分子和机制基础在很大程度上尚不清楚。在这里，我们证明了机械敏感 K+ 通道 TRAAK 的超声激活具有亚毫秒动力学，其程度与典型的机械激活相当。单通道记录揭示了超声和机械激活的共同基础，其中刺激分级的长时间闭合不稳定和促进完全电导打开。在没有其他细胞成分的情况下，超声波能量通过膜传导至 TRAAK，可能会增加膜张力以促进通道开放。我们进一步证明了神经元表达 TRAAK 的超声调制。这些结果表明机械敏感通道是对超声波的生理反应的基础，并且可以作为基因靶向细胞的声神经调节的声发生致动器。
Ultrasound stimulation modulates the electrical activity of excitable cells, including in neurons of the brain and central nervous system. Compared to other neuromodulatory techniques, ultrasound offers several advantages; for example, it can be noninvasively transmitted through the skull and focused to deep brain regions. However, the molecular basis underlying the effects of ultrasound on neural activity is not known. Here, we show that ultrasound activates the mechanosensitive ion channel TRAAK through the membrane in a manner analogous to canonical mechanical activation, likely by increasing membrane tension to promote channel opening. These results suggest mechanosensitive channels underlie physiological responses to ultrasound and could serve as tools for acoustic neuromodulation of genetically targeted cells. Ultrasound modulates the electrical activity of excitable cells and offers advantages over other neuromodulatory techniques; for example, it can be noninvasively transmitted through the skull and focused to deep brain regions. However, the fundamental cellular, molecular, and mechanistic bases of ultrasonic neuromodulation are largely unknown. Here, we demonstrate ultrasound activation of the mechanosensitive K+ channel TRAAK with submillisecond kinetics to an extent comparable to canonical mechanical activation. Single-channel recordings reveal a common basis for ultrasonic and mechanical activation with stimulus-graded destabilization of long-duration closures and promotion of full conductance openings. Ultrasonic energy is transduced to TRAAK through the membrane in the absence of other cellular components, likely increasing membrane tension to promote channel opening. We further demonstrate ultrasonic modulation of neuronally expressed TRAAK. These results suggest mechanosensitive channels underlie physiological responses to ultrasound and could serve as sonogenetic actuators for acoustic neuromodulation of genetically targeted cells.
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影响因子：
--
作者：
Bronstein JM;Tagliati M;Alterman RL;Lozano AM;Volkmann J;Stefani A;Horak FB;Okun MS;Foote KD;Krack P;Pahwa R;Henderson JM;Hariz MI;Bakay RA;Rezai A;Marks WJ Jr;Moro E;Vitek JL;Weaver FM;Gross RE;DeLong MR
通讯作者：
DeLong MR
影响因子：
16.2
作者：
Guo, Hongsun;Hamilton, Mark, II;Lim, Hubert H.
通讯作者：
Lim, Hubert H.
DOI：
10.1126/science.aan5544
发表时间：
2017-09-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Deisseroth K;Hegemann P
通讯作者：
Hegemann P
DOI：
10.1073/pnas.1320768111
发表时间：
2014-03-04
影响因子：
11.1
作者：
Brohawn, Stephen G.;Su, Zhenwei;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
影响因子：
--
作者：
Harvey, EN
通讯作者：
Harvey, EN