1. Ultrasound activates mechanosensitive TRAAK K + channels through the lipid membrane
- Author
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Karthika Gopakumar, Hillel Adesnik, Stephen G. Brohawn, Ben Sorum, and Robert A. Rietmeijer
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0301 basic medicine ,Potassium Channels ,Mechanotransduction ,Xenopus ,Mechanotransduction, Cellular ,Mice ,0302 clinical medicine ,Models ,mechanosensation ,Ultrasonics ,Lipid bilayer ,Tandem Pore Domain ,K channels ,Cerebral Cortex ,Neurons ,Multidisciplinary ,ultrasound ,Chemistry ,Ultrasound ,Temperature ,Biological Sciences ,K2P ion channels ,Neuromodulation (medicine) ,Membrane ,neuromodulation ,Biomedical Imaging ,Mechanosensitive channels ,Ion Channel Gating ,1.1 Normal biological development and functioning ,Bioengineering ,sonogenetics ,Models, Biological ,Membrane Lipids ,03 medical and health sciences ,Potassium Channels, Tandem Pore Domain ,Underpinning research ,Animals ,Humans ,Mechanosensation ,business.industry ,Neurosciences ,Biological ,Kinetics ,030104 developmental biology ,Oocytes ,Biophysics ,Ultrasonic sensor ,Cellular ,business ,030217 neurology & neurosurgery ,Neuroscience - Abstract
Significance 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.
- Published
- 2021
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