Ultrasound modulates the electrical activity of excitable cells and offers advantages over other neuromodulatory techniques; for example, it can be non-invasively transmitted through 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 sub-millisecond 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 longduration closures and promotion of full conductance openings. Ultrasonic energy is transduced to TRAAK directly 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 provides a framework for developing channel-based sonogentic actuators for acoustic neuromodulation of genetically targeted cells.

中文翻译：

---

超声直接通过脂质膜激活机械敏感性TRAAK K +通道

超声调节可兴奋细胞的电活动，并提供优于其他神经调节技术的优势；例如，它可以通过颅骨无创地传播并集中到大脑深处。但是，超声神经调节的基本细胞，分子和机制基础尚不清楚。在这里，我们证明了机械敏感的K +通道TRAAK的超声激活具有亚毫秒级的动力学，其程度可与规范的机械激活相媲美。单通道记录揭示了超声和机械激活的共同基础，其中刺激性的持久闭合装置的稳定性逐渐降低，并促进了完整的电导开口。在没有其他细胞成分的情况下，超声波能量直接通过膜直接传导至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的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，并为开发基于通道的声波致动器提供了框架，以用于遗传靶向细胞的声神经调节。