Ultrasound modulates ion channel currents.
Transcranial focused ultrasound (US) has been demonstrated to stimulate neurons in animals and humans, but the mechanism of this effect is unknown. It has been hypothesized that US, a mechanical stimulus, may mediate cellular discharge by activating mechanosensitive ion channels embedded within cellular membranes. To test this hypothesis, we expressed potassium and sodium mechanosensitive ion channels (channels of the two-pore-domain potassium family (K2P) including TREK-1, TREK-2, TRAAK; NaV1.5) in the Xenopus oocyte system. Focused US (10 MHz, 0.3-4.9 W/cm(2)) modulated the currents flowing through the ion channels on average by up to 23%, depending on channel and stimulus intensity. The effects were reversible upon repeated stimulation and were abolished when a channel blocker (ranolazine to block NaV1.5, BaCl2 to block K2P channels) was applied to the solution. These data reveal at the single cell level that focused US modulates the activity of specific ion channels to mediate transmembrane currents. These findings open doors to investigations of the effects of  US on ion channels expressed in neurons, retinal cells, or cardiac cells, which may lead to important medical applications. The findings may also pave the way to the development of sonogenetics: a non-invasive, US-based analogue of optogenetics.
Department of Molecular and Cellular Physiology, 279 Campus Drive, Stanford University, Stanford, CA 94305, USA.|Department of Biomedical Engineering, One Brookings Dr., Washington University in St. Louis, St. Louis, MO 63130, USA.
Jan
J
Kubanek
Department of Biomedical Engineering, One Brookings Dr., Washington University in St. Louis, St. Louis, MO 63130, USA.
Jingyi
J
Shi
Department of Internal Medicine, 4320 Forest Park Ave, Washington University, St. Louis, MO 63110, USA.
Jon
J
Marsh
Department of Biomedical Engineering, 2200 Bonisteel Blvd.,University of Michigan, Ann Arbor, MI 48109, USA.
Di
D
Chen
Department of Biomedical Engineering, 2200 Bonisteel Blvd.,University of Michigan, Ann Arbor, MI 48109, USA.
Cheri
C
Deng
Department of Biomedical Engineering, One Brookings Dr., Washington University in St. Louis, St. Louis, MO 63130, USA.
Jianmin
J
Cui
D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism / Q000502:physiology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism; D000069458:Ranolazine / Q000494:pharmacology; D013696:Temperature; D017585:Ultrasonography, Doppler, Transcranial; D061567:Voltage-Gated Sodium Channel Blockers / Q000494:pharmacology; D014981:Xenopus / Q000254:growth & development / Q000502:physiology*
D017609:Barium Compounds; D002712:Chlorides; D062554:NAV1.5 Voltage-Gated Sodium Channel; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D061567:Voltage-Gated Sodium Channel Blockers; C103742:potassium channel protein TREK-1; C024986:barium chloride; D000069458:Ranolazine