Ultrasound-Induced Currents in Planar Lipid Blayers: Origins and Potential Physiological Significance

Abstract

Low-intensity focused ultrasound shows great promise for non-invasive, spatially resolved modulation of neural activity in vivo. To determine the mechanisms involved in ultrasonic modulation of neural activity and guide the development of this technology, we have been investigating the effects of ultrasound on protein-free planar lipid bilayers. Previously, we reported that ultrasound causes decaying current oscillations in planar bilayers at the onset and offset of the stimulus. These on and off responses are of opposite polarity but otherwise identical. Here, we report that if the rise time of the ultrasound pulse is prolonged, the on response is resolved into two distinct components: a sigmoidal component during the rise time and a damped oscillating component once the pulse reaches its final value. This result suggests that changes in ultrasound intensity during the rise time of the pulse may be important in determining the response to ultrasound in vivo, and is consistent with the observation that pulsed ultrasound is more effective than continuous ultrasound in modulating neural activity. To investigate further the origins of the on/off behavior, we used an optical interferometer to measure the velocity of the ultrasound-induced movement (acoustic streaming) in the solution surrounding the bilayer. We find that the time course of the ultrasound-induced current matches the time course of the streaming velocity, with a ratio of 162 pA/(mm/s). This acoustic streaming is probably due to the action of ultrasonic radiation force. To explore the potential physiological relevance of these effects, and to obtain further mechanistic insight, we are investigating the response of planar bilayers to ultrasound under current-clamp. In preliminary experiments, we find that ultrasound pulses with intensity comparable to those used in vivo produce voltage changes that would be sufficient to initiate an action potential.