Temporally-specific modification of myelinated axon excitability in vitro following a single ultrasound pulse
Richard T. Mihran, Frank S. Barnes, Howard Wachtel
Ultrasound in Medicine & Biology 1990, 16, 297-309 · 10.1016/0301-5629(90)90008-z
Abstract
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.
Abstract via europepmc.
Exposures
Exposure 1: 2 MHz ultrasound pulses to excised frog sciatic nerve
Target: excised nerve — “sciatic nerve”
Device: Olympus / Panametrics · Panametrics · V304 ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 2,000 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 0.0005 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 100, 800swept | ✓✓✓⚑ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not applicable | |
| In-situ pressure (kPa) | not applicable | |
| In-situ Isppa (W/cm²) | not applicable | |
| In-situ Ispta (W/cm²) | not applicable |
A single, focused ultrasound pulse (500 microseconds duration) was applied to a segment of excised sciatic nerve bathed in Ringers solution, and the relative excitability of the nerve (via a separately evoked compound action potential) was assessed at latencies from 0 to 100 ms post-pulse. The 3-mm defocused spot size was used in most experiments; additional experiments varied the spot size (1.25-2.88 mm half-power width) at constant peak intensity.
Exposure 2: 4 MHz ultrasound pulses to excised frog sciatic nerve
Target: excised nerve — “sciatic nerve”
Device: Olympus / Panametrics · Panametrics · V304 ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 4,000 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 0.0005 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 100, 800swept | ✓✓✓⚑ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not applicable | |
| In-situ pressure (kPa) | not applicable | |
| In-situ Isppa (W/cm²) | not applicable | |
| In-situ Ispta (W/cm²) | not applicable |
The frequency dependence of the excitability effect was tested using 4 MHz ultrasound pulses of comparable duration and intensity range to the 2 MHz condition, with the nerve trunk repositioned in the focal region so that the half-power spot size was held constant across frequencies.
Exposure 3: 7 MHz ultrasound pulses to excised frog sciatic nerve
Target: excised nerve — “sciatic nerve”
Device: Olympus / Panametrics · Panametrics · V304 ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 7,000 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 0.0005 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 100, 800swept | ✓✓✓⚑ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not applicable | |
| In-situ pressure (kPa) | not applicable | |
| In-situ Isppa (W/cm²) | not applicable | |
| In-situ Ispta (W/cm²) | not applicable |
The frequency dependence of the excitability effect was tested using 7 MHz ultrasound pulses of comparable duration and intensity range to the 2 MHz condition, with the nerve trunk repositioned in the focal region so that the half-power spot size was held constant across frequencies.
Flags from extraction
exposures[0].free_field.isppa_w_cm2— The paper reports 'peak intensities' without specifying whether this is spatial-peak pulse-average (ISPPA), temporal-peak, or another convention; recorded as isppa_w_cm2.exposures[1].free_field.isppa_w_cm2— The 4 MHz condition is described only as having 'comparable duration and range of intensities' to the 2 MHz condition (100-800 W/cm2, 500 microseconds); no independent numeric values are given for 4 MHz specifically.exposures[2].free_field.isppa_w_cm2— The 7 MHz condition is described only as having 'comparable duration and range of intensities' to the 2 MHz condition (100-800 W/cm2, 500 microseconds); no independent numeric values are given for 7 MHz specifically.n_subjects— The paper never states the total number of nerve preparations used across the reported experiments.