Abstract
Ultrasound (US) can modulate the electrical activity of the excitable tissues, but
the mechanisms underlying this effect are not understood at the molecular level or
in terms of the physical modality through which US exerts its effects. Here, we report
an experimental system that allows for stable patch-clamp recording in the presence
of US at 43 MHz, a frequency known to stimulate neural activity. We describe the effects
of US on two ion channels proposed to be involved in the response of excitable cells
to US: the mechanosensitive Piezo1 channel and the voltage-gated sodium channel NaV1.2. Our patch-clamp recordings, together with finite-element simulations of acoustic
field parameters indicate that Piezo1 channels are activated by continuous wave US
at 43 MHz and 50 or 90 W/cm2 through cell membrane stress caused by acoustic streaming. NaV1.2 channels were not affected through this mechanism at these intensities, but their
kinetics could be accelerated by US-induced heating.
Key Words
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References
- Xerocytosis is caused by mutations that alter the kinetics of the mechanosensitive channel PIEZO1.Proc Natl Acad Sci USA. 2013; 110: E1162-E1168
- Outliers in statistical data.Wiley and Sons, Chichester NY1994
- Mechanosensitivity of Nav1.5, a voltage-sensitive sodium channel.J Physiol. 2010; 588: 4969-4985
- Mechanosensitivity is mediated directly by the lipid membrane in TRAAK and TREK1 K+ channels.Proc Natl Acad Sci USA. 2014; 111: 3614-3619
- A review of low-intensity focused ultrasound pulsation.Brain Stimul. 2011; 4: 125-136
- Handbook of chemistry and physics.Chemical Rubber Compnay, Cleveland, OH1965
- Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels.Science. 2010; 330: 55-60
- Piezo proteins are pore-forming subunits of mechanically activated channels.Nature. 2012; 483: 176-181
- Nanoscale organization of the MEC-4 DEG/ENaC sensory mechanotransduction channel in Caenorhabditis elegans touch receptor neurons.J Neurosci. 2007; 27: 14089-14098
- Effects of pulsed ultrasound on the frog heart: III. The radiation force mechanism.Ultrasound Med Biol. 1997; 23: 275-285
- Endogenous piezo1 can confound mechanically activated channel identification and characterization.Neuron. 2017; 94: 266-270
- Radiation pressure and acoustic streaming.in: Duck F.A. Baker A.C. Starritt H.C. Ultrasound in medicine. Institute of Physics Publishing, Philadelphia, PA1998
- Computer control of microscopes using µManager.Curr Protoc Mol Biol. 2010; (Chapter:Unit14.20)https://doi.org/10.1002/0471142727.mb1420s92
- The effect of temperature on the sodium and potassium permeability changes in myelinated nerve fibres of Xenopus laevis.J Physiol. 1963; 169: 431-437
- Production of reversible changes in the central nervous system by ultrasound.Science. 1958; 127: 83-84
- Heat-capacity and other thermodynamic properties of linear macromolecules. V. Polystyrene.J Phys Chem Ref Data. 1982; 11: 313-325
- Application of focused ultrasound for the stimulation of neural structures.Ultrasound Med Biol. 1996; 22: 179-192
- Modulation of GTPase activity of G proteins by fluid shear stress and phospholipid composition.Proc Natl Acad Sci USA. 1998; 95: 2515-2519
- Ultrasound hyperthermia and the prediction of heating.in: Duck F.A. Baker A.C. Starritt H.C. Ultrasound and medicine. Institute of Physics Publishing, Philadelphia, PA1998
- Handbook of plastics technologies: The complete guide to properties and performance.McGraw-Hill, New York, NY2006
- Effects of high frequency sound waves on heart muscle and other irritable tissues.Am J Physiol. 1929; 91 (294–90)
- Elastic properties of lipid bilayers: Theory and possible experiments.Z Naturforsch [C]. 1973; 28: 693-703
- Measurement of current-voltage relations in the membrane of the giant axon of Loligo.J Physiol. 1952; 116: 424-448
- Fluorescence response of human HER2+ cancer- and MCF-12 F normal cells to 200 MHz ultrasound microbeam stimulation: A preliminary study of membrane permeability variation.Ultrasonics. 2012; 52: 803-808
- Non-contact high-frequency ultrasound microbeam stimulation for studying mechanotransduction in human umbilical vein endothelial cells.Ultrasound Med Biol. 2014; 40: 2172-2182
- Cell deformation by single-beam acoustic trapping: A promising tool for measurements of cell mechanics.Sci Rep. 2016; 6: 27238
- Focused ultrasound-mediated non-invasive brain stimulation: Examination of sonication parameters.Brain Stimul. 2014; 7: 748-756
- Suppression of EEG visual-evoked potentials in rats through neuromodulatory focused ultrasound.Neuroreport. 2015; 26: 211-215
- Effective parameters for ultrasound-induced in vivo neurostimulation.Ultrasound Med Biol. 2013; 39: 312-331
- Localization of ultrasound-induced in vivo neurostimulation in the mouse model.Ultrasound Med Biol. 2014; 40: 1512-1522
- Introduction to practical fluid flow.Butterworth-Heinemann, Boston, MA2002
- Intramembrane cavitation as a unifying mechanism for ultrasound-induced bioeffects.Proc Natl Acad Sci USA. 2011; 108: 3258-3263
- Ultrasound modulates ion channel currents.Sci Rep. 2016; 6: 24170
- Theory of elasticity.Pergamon Press, Oxford, UK1986
- Image-guided transcranial focused ultrasound stimulates human primary somatosensory cortex.Sci Rep. 2015; 5: 8743
- Image-guided focused ultrasound-mediated regional brain stimulation in sheep.Ultrasound Med Biol. 2016; 42: 459-470
- Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans.Nat Neurosci. 2014; 17: 322-329
- Mechanical sensitivity of Piezo1 ion channels can be tuned by cellular membrane tension.Elife. 2015; 4: e12088
- Increased anatomical specificity of neuromodulation via modulated focused ultrasound.PLoS ONE. 2014; 9 (e86939)
- Precise neural stimulation in the retina using focused ultrasound.J Neurosci. 2013; 33: 4550-4560
- 2013 Origins of ultrasound neural stimulation in the retina.(Program No. 218.11. 2013 Society for Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience)2013 (Online)
- 2016 Physical mechanisms of ultrasonic neurostimulation in the In vitro retina.(Program No. 353.05. 2016 Society for Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience)2016 (Online)
- Focused ultrasound-mediated suppression of chemically-induced acute epileptic EEG activity.BMC Neurosci. 2011; 12: 23
- Assessment of potential stimuli for mechano-dependent gating of MscL: Effects of pressure, tension, and lipid headgroups.Biochemistry. 2005; 44: 12239-12244
- Nav channel mechanosensitivity: Activation and inactivation accelerate reversibly with stretch.Biophys J. 2007; 93: 822-833
- Acoustic streaming.in: Hamilton M.F. Blackstock D.T. Nonlinear acoustics. Acoustic Society of America, Melville, NY2008
- Ultrasound-biophysics mechanisms.Prog Biophys Mol Biol. 2007; 93: 212-255
- Acoustics: An introduction to its physical principles and applications.Acoustic Society of America, Melville, NY1994
- Intramembrane cavitation as a predictive bio-piezoelectric mechanism for ultrasonic brain stimulation.Phys Rev X. 2013; 4: 011004
- Cell-type-selective effects of intramembrane cavitation as a unifying theoretical framework for ultrasonic neuromodulation.eNeuro. 2016; 3 (ENEURO.0136-15.2016)
- Dynamic response of model lipid membranes to ultrasonic radiation force.PLoS ONE. 2013; 8: e77115
- 2016 Focused Ultrasound at 43 MHz Inhibits Action Potential Firing in Hippocampal Brain Slices.(Program No. 561.13. 2016 Society for Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience)2016 (Online)
- Biomedical applications of radiation force of ultrasound: Historical roots and physical basis.Ultrasound Med Biol. 2010; 36: 1379-1394
- Acoustic neuromodulation from a basic science prospective.J Ther Ultrasound. 2016; 4: 17
- Changes in single K(+) channel behavior induced by a lipid phase transition.Biophys J. 2010; 99: 3675-3683
- Approximate material properties in isotropic materials.IEEE Trans Son Ultrason. 1985; 32: 381-394
- Infrared light excites cells by changing their electrical capacitance.Nat Commun. 2012; 3: 736
- Quantitative video microscopy of patch clamped membranes stress, strain, capacitance, and stretch channel activation.Biophys J. 1991; 59: 722-728
- Biophysics and structure of the patch and the gigaseal.Biophys J. 2009; 97: 738-747
- A large-conductance mechanosensitive channel in E. coli encoded by mscL alone.Nature. 1994; 368: 265-268
- Piezo1 channels are inherently mechanosensitive.Cell Rep. 2016; 17: 1739-1746
- Interaction of ultrasound and model: Analyses and predictions.J Phys Chem. 1992; 96: 3548-3555
- Transcranial pulsed ultrasound stimulates intact brain circuits.Neuron. 2010; 66: 681-694
- Noninvasive neuromodulation with ultrasound? A continuum mechanics hypothesis.Neuroscientist. 2011; 17: 25-36
- Remote excitation of neuronal circuits using low-intensity, low-frequency ultrasound.PLoS ONE. 2008; 3: e3511
- Lipid bilayer mechanics in a pipette with glass-bilayer adhesion.Biophys J. 2011; 101: 1913-1920
- Piezo channels: From structure to function.Pflugers Arch. 2015; 467: 95-99
- Membrane trauma and Na+ leak from Nav1.6 channels.Am J Physiol Cell Physiol. 2009; 297: C823-C834
- Touch, tension, and transduction—The function and regulation of piezo ion channels.Trends Biochem Sci. 2017; 42: 57-71
- Rapid temperature jump by infrared diode laser irradiation for patch-clamp studies.Biophys J. 2009; 96: 3611-3619
- Frequency dependence of ultrasound neurostimulation in the mouse brain.Ultrasound Med Biol. 2016; 42: 1512-1530
- Focused ultrasound modulates region-specific brain activity.Neuroimage. 2011; 56: 1267-1275
- Influence of the pressure field distribution in transcranial ultrasonic neurostimulation.Med Phys. 2013; 40: 082902
- Ankyrin repeats convey force to gate the NOMPC mechanotransduction channel.Cell. 2015; 162: 1391-1403
Article info
Publication history
Published online: March 07, 2018
Accepted:
December 22,
2017
Received in revised form:
December 19,
2017
Received:
September 11,
2017
Identification
Copyright
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