Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 118, Issue 6, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2006980118
Keywords
mechanosensation; ultrasound; K2P ion channels; neuromodulation; sonogenetics
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Funding
- New York Stem Cell Foundation
- National Institute of General Medical Sciences [DP2GM123496-01]
- McKnight Foundation Scholar Award
- Klingenstein-Simons Foundation Fellowship Award
- Rose-Hill Innovator Award
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Ultrasound has been shown to modulate the electrical activity of excitable cells by activating mechanosensitive channels, which may have implications for targeted neuromodulation in the future. This discovery provides a new theoretical basis for the application of ultrasound in neuroscience.
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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