Abstract
Modern technologies enable deep tissue focusing of nanosecond pulsed electric field (nsPEF) for non-invasive nerve and muscle stimulation. However, it is not known if PEF orders of magnitude shorter than the activation time of voltage-gated sodium channels (VGSC) would evoke action potentials (APs). One plausible scenario requires the loss of membrane integrity (electroporation) and resulting depolarization as an intermediate step. We report, for the first time, that the excitation of a peripheral nerve can be accomplished by 12-ns PEF without electroporation. 12-ns stimuli at 4.1–11 kV (3.3–8.8 kV/cm) evoked APs similarly to conventional stimuli (100–250 μs, 1–5 V, 103–515 V/m), except for having higher selectivity for the faster nerve fibers. Nerves sustained repeated tetanic stimulations (50 Hz or 100 Hz for 1 min) alternately by 12-ns PEF and by conventional pulses. Such tetani caused a modest AP decrease, to a similar extent for both types of stimuli. Nerve refractory properties were not affected. The lack of cumulative damages even from tens of thousands of 12-ns stimuli and the similarities with the conventional stimulation prove VGSC activation by nsPEF without nerve membrane damage.
Highlights
In past decades, neurostimulation has gained attention in medical applications where conventional pharmacological approaches become ineffective or are not tolerated by patients
We found that the 12-ns stimuli can elicit compound action potentials (CAPs) to conventional stimuli, with the threshold of 4.1–6 kV (3.3–4.8 kV/cm)
The refractory period was always assessed by the conventional stimuli, while using either nanosecond pulsed electric field (nsPEF) or conventional stimuli for the tetanus. These measurements established no effect of either conventional or nsPEF tetanic stimulation of the refractory properties of the nerve (Fig. 5), providing further proof that 12-ns PEF stimulation did not damage the nerve. This is the first study which tested the ability of 12-ns electric pulses to stimulate a peripheral nerve
Summary
Neurostimulation has gained attention in medical applications where conventional pharmacological approaches become ineffective or are not tolerated by patients. Recent advancements in pulsed power physics and engineering have extended the range of electric stimuli to nano- and sub-nanosecond pulse durations[8,9,10,11,12,13,14]. Conventional electrostimulation by milli- and microsecond pulses relies on the movement of ions to build up a high potential difference at the membrane interface. This process, known as Maxwell-Wagner ionic polarization, amplifies the externally applied electric field more than 1,000-fold, so that the transmembrane potential threshold can be reached even with low voltage stimuli. The excitation was judged by a muscle twitch and was assumed to result from stimulation www.nature.com/scientificreports/
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