TABLE 3.

Current sonogenetics studies on MS proteins.

MS protein family	Study	MS protein(s)	Ion selectivity	Target species	Ultrasound parameters	Neuromodulation	Associated mechanism	Conclusion
TRP channel	Ibsen et al. (2015)	TRP-4, a TRPN subfamily channel	Mechano-gated non-selective cation transduction	C. elegans	Single 10-ms, 2.25 MHz sine wave ultrasound with peak negative pressure of 0–0.9 MPa	Excitation	US-microbubble amplification	TRP-4 might be activated in response to US with peak negative pressure levels and modifies neurons by increasing microbubbles, resulting in the modulation of C. elegans behavior
MS channel	Ye et al. (2018)	MscL, a 3-Ns homotetrameric or homopentameric MS channel	Mechano-gated non-selective molecules: calcein efflux	Rat hippocampal CA1/CA3 neurons	Ultrasound transducer frequency:29.92 MHz Peak negative pressure: 0.12–0.45 Pa PRF: 1, 5, 10 Hz Duration: 50, 100, 200, 300, 400 ms	Excitation	Force-from-lipid theory	I92L mutant of MscL channel can be opened to control neuronal activities by using US to change membrane mechanical sensitivity
	Babakhanian et al. (2018)			In vitro proteoliposome model	Ultrasound transducer frequency: 0.5 MHz LIFU PRF: 1 kHz DC: 60%, 80% and CW Duration: 0, 5, 10 and 20 min	/	MscL can inhibit pore formation through LIFU modulation and membrane perturbation independent of channel gating	Compared with another two voltage-gated channels (KvAP and NaK2K F92A), the MscL channel can inhibit pore formation through LIFU modulation and membrane perturbation independent of channel gating
	Zhang et al. (2012) and Song et al. (2017)	TtMscS, a 2-Ns homotetrameric or homopentameric MS channel in T. tengcongensis	Mechano-gated anion over cation influx	T. tengcongensis	/	/	/	/
	Martinac et al. (1987)	EcMscS, a 2-Ns homotetrameric or homopentameric MS channel in E. coli	Mechano-gated anion influx	E. coli	/	/	/	/
DEG/ENaCs/ASIC channel	Kubanek et al. (2018)	MEC-4	Non-voltage-gated Na+ influx	C. elegans	Ultrasound transducer frequency: 10 MHz Peak negative pressure: 0-1 MPa PRF: 30, 100, 300, 1k, 3k, 10 kHz DC: 5, 10, 25, 50, 75, 100% Duration: 50, 100, 200, 300, 400 ms	Excitation	Cavitation, oscillations in the incident tissue and acoustic radiation forces	Ultrasound can stimulate neurons via MEC-4-dependent MS ion channels rather than via a thermal effect
VGCs channel	Tyler et al. (2008)	Nav and Cav	Nav: Voltage-gated Na+ influx Cav: voltage-gated Ca2+ influx	Ex vivo brains	Ultrasound transducer frequency: 0.44–0.67 MHz LIFU IPA: 2.9 W/cm2 ITA: 23 mW/cm2 PRF: 0–100 Hz	Excitation	Channel gating	US can remotely modulate brain circuit activity by activating voltage-gated sodium and calcium channels
	Kubanek et al. (2016)	Nav	Voltage-gated Na+ influx	Xenopus oocytes	Ultrasound transducer frequency: 10 MHz Peak negative pressure: 425 kPa–1.75 MPa PRF: 1 kHz DC: 5% Duration: 50 μs	Excitation	Channel gating	US may lead to excitation in cells that predominantly express Na+ US-sensitive ion channels
K2P channel	Kubanek et al. (2016)	TREK-1, TREK-2, TRAAK	Mechano-gated K+ efflux at −70, −10, +50 mV of membrane voltage	Xenopus oocytes	Ultrasound transducer frequency: 10 MHz Peak negative pressure: 120 kPa–240 kPa Duration: 0, 1, 2 s	Inhibition	Channel gating	US may inhibit cells that predominantly express K+ US-sensitive ion channels
Piezo channel	Qiu et al. (2019)	Piezo1	Mechano-gated cation: Ca2+ influx	In vitro mouse neuronal cells	Ultrasound transducer frequency: 500 kHz LIFU Peak negative pressure: 0.1, 0.3, 0.5MPa PRF: 1 kHz DC: 40% Duration: 20 min	Excitation	Channel gating	Activation of primary neurons in vitro can be reduced through the inhibition of Piezo1 activity stimulated by low-frequency US without microbubbles
	Liao et al. (2019)			In vitro HEK293T cells	Ultrasound transducer frequency: 30 MHz vertically deployed surface acoustic wave (VD-SAW) Peak negative pressure: 1.6 MPa PRF: 2 Hz, 200 Hz DC: 20% Duration: 60 s	/	/	/