Ultrasound activates mechanosensitive TRAAK K+ channels through the lipid membrane

Ben Sorum, Robert A. Rietmeijer, Karthika Gopakumar, Hillel Adesnik, Stephen G. Brohawn

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere2006980118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number6
DOIs
StatePublished - Feb 9 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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