Temporally-specific modification of myelinated axon excitability in vitro following a single ultrasound pulse

Single, short-duration, low-energy pulses of ultrasound were found to elicit distinct modifications of the electrical excitability of myelinated frog sciatic nerve in vitro in a window extending 40-50 ms after pulse termination. These modifications include both enhancement and suppression of relative excitability, the sequence of which generally follows one of two distinct temporal response patterns. The ultrasound pulses were focused, 2-7 MHz, of 500-microseconds duration, and of peak intensities of 100-800 W/cm2. Total absorbed pulse energies were generally less than 100 mJ/g, corresponding to local temperature rises of the nerve trunk of no more than 0.025 degrees C per pulse, thereby precluding bulk heating as a basis of this effect. The observed effects cannot be elicited using either a subthreshold square wave or RF electrical prestimulus, suggesting a unique form of receptivity of the nerve trunk to mechanical perturbation. We present evidence that the low-frequency radiation pressure transient accompanying the envelope of the acoustic pulse is the active parameter in this phenomenon, and postulate that it may act by the gating of stretch-sensitive channels, which have been recently reported in a variety of cell membranes. These results may demonstrate that stretch-sensitive channels in neural membrane can serve to functionally modulate neuro-electric signals normally mediated by voltage-dependent channels, a finding which could suggest new clinical applications of high peak-power, low-total-energy pulsed ultrasound.