Tension activation of mechanosensitive two-pore domain K+ channels TRAAK, TREK-1, and TREK-2

Ben Sorum, Trevor Docter, Vincent Panico, Robert A. Rietmeijer and Stephen G. Brohawn ()
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Ben Sorum: University of California Berkeley
Trevor Docter: University of California Berkeley
Vincent Panico: University of California Berkeley
Robert A. Rietmeijer: University of California Berkeley
Stephen G. Brohawn: University of California Berkeley

Nature Communications, 2024, vol. 15, issue 1, 1-9

Abstract: Abstract TRAAK, TREK-1, and TREK-2 are mechanosensitive two-pore domain K+ (K2P) channels that contribute to action potential propagation, sensory transduction, and muscle contraction. While structural and functional studies have led to models that explain their mechanosensitivity, we lack a quantitative understanding of channel activation by membrane tension. Here, we define the tension response of mechanosensitive K2Ps using patch-clamp recording and imaging. All are low-threshold mechanosensitive channels (T10%/50% 0.6-2.7 / 4.4-6.4 mN/m) with distinct response profiles. TRAAK is most sensitive, TREK-1 intermediate, and TREK-2 least sensitive. TRAAK and TREK-1 are activated broadly over a range encompassing nearly all physiologically relevant tensions. TREK-2, in contrast, activates over a narrower range like mechanosensitive channels Piezo1, MscS, and MscL. We further show that low-frequency, low-intensity focused ultrasound increases membrane tension to activate TRAAK and MscS. This work provides insight into tension gating of mechanosensitive K2Ps relevant to understanding their physiological roles and potential applications for ultrasonic neuromodulation.

Date: 2024
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DOI: 10.1038/s41467-024-47208-5

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