Frequency-dependent interaction of ultrashort E-fields with nociceptor membranes and proteins

Jiang, Nan; Cooper, Brian Y.

doi:10.1002/bem.20620

Cited by 35 publications

(20 citation statements)

References 55 publications

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“…4,5 Jiang and Cooper demonstrated that a single, 12 ns nsPEF at 403 V∕cm was capable of activating skin nociceptors. 14 They were able to demonstrate this same effect at 100 pulses delivered at 4000 Hz with very low voltages (16.7 V∕cm).…”

Section: Introductionmentioning

confidence: 77%

Nanosecond pulsed electric field thresholds for nanopore formation in neural cells

Roth¹,

Tolstykh

Payne

et al. 2013

J. Biomed. Opt

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Abstract. The persistent influx of ions through nanopores created upon cellular exposure to nanosecond pulse electric fields (nsPEF) could be used to modulate neuronal function. One ion, calcium (Ca 2þ ), is important to action potential firing and regulates many ion channels. However, uncontrolled hyper-excitability of neurons leads to Ca 2þ overload and neurodegeneration. Thus, to prevent unintended consequences of nsPEF-induced neural stimulation, knowledge of optimum exposure parameters is required. We determined the relationship between nsPEF exposure parameters (pulse width and amplitude) and nanopore formation in two cell types: rodent neuroblastoma (NG108) and mouse primary hippocampal neurons (PHN). We identified thresholds for nanoporation using Annexin V and FM1-43, to detect changes in membrane asymmetry, and through Ca 2þ influx using Calcium Green. The ED50 for a single 600 ns pulse, necessary to cause uptake of extracellular Ca 2þ , was 1.76 kV∕cm for NG108 and 0.84 kV∕cm for PHN. At 16.2 kV∕cm, the ED50 for pulse width was 95 ns for both cell lines. Cadmium, a nonspecific Ca 2þ channel blocker, failed to prevent Ca 2þ uptake suggesting that observed influx is likely due to nanoporation. These data demonstrate that moderate amplitude single nsPEF exposures result in rapid Ca 2þ influx that may be capable of controllably modulating neurological function. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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Section: Introductionmentioning

confidence: 77%

Nanosecond pulsed electric field thresholds for nanopore formation in neural cells

Roth¹,

Tolstykh

Payne

et al. 2013

J. Biomed. Opt

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“…With this strategy, measurement of membrane currents was possible as soon as 5 s after NEP exposure. Jiang and Cooper (2012) used an entirely different strategy in their studies of NEP effects on sensory neurons. During exposure of patched neurons to high-intensity NEP(s), the patch clamp pre-amplifier was physically disconnected from the amplifier during the time of pulse delivery.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Monitoring of Nanosecond Electric Pulse-Evoked Membrane Conductance Changes in Whole-Cell Patch Clamp Experiments

et al. 2016

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Patch clamp electrophysiology serves as a powerful method for studying changes in plasma membrane ion conductance induced by externally applied high-intensity nanosecond electric pulses (NEPs). This paper describes an enhanced monitoring technique that minimizes the length of time between pulse exposure and data recording in a patch-clamped excitable cell. Whole-cell membrane currents were continuously recorded up to 11 ms before and resumed 8 ms after delivery of a 5-ns, 6 MV/m pulse by a pair of tungsten rod electrodes to a patched adrenal chromaffin cell maintained at a holding potential of -70 mV. This timing was achieved by two sets of relay switches. One set was used to disconnect the patch pipette electrode from the pre-amplifier and connect it to a battery to maintain membrane potential at -70 mV, and also to disconnect the reference electrode from the amplifier. The other set was used to disconnect the electrodes from the pulse generator until the time of NEP/sham exposure. The sequence and timing of both sets of relays were computer-controlled. Using this procedure, we observed that a 5-ns pulse induced an instantaneous inward current that decayed exponentially over the course of several minutes, that a second pulse induced a similar response, and that the current was carried, at least in part, by Na. This approach for characterizing ion conductance changes in an excitable cell in response to NEPs will yield information essential for assessing the potential use of NEP stimulation for therapeutic applications.

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“…Several studies reported that a single high-amplitude stimulus of 350- 100-, 12-, 5-, 4-, and even 1-ns duration can activate nerve, muscle, and endocrine cells [13–18]. The thresholds varied for the different targets, but overall they expectedly became higher for shorter stimuli.…”

Section: Introductionmentioning

confidence: 99%

“…However, high-rate nsEP trains could elicit action potentials even at low amplitudes. For example, delivering 12-ns pulses in 25 ms, 4 kHz bursts reduced the threshold for isolated nociceptor neurons from 0.4 to 0.016 kV/cm [13]. …”

Section: Introductionmentioning

confidence: 99%

“…The authors argued that the mechanism of action potential generation in neurons [13] and in the neuromuscular preparation [15] was not different from the conventional electrostimulation with longer EP and did not involve electroporation. However, the absence of electroporation was either just a conjecture from the fact that the threshold for 1-ns stimuli fell roughly on the same strength-duration curve as the data for longer pulses [15], or was based on the lack of the uptake of propidium iodide [13] (which is not a sensitive marker of nanoporation [19, 20]).…”

Section: Introductionmentioning

confidence: 99%

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Cell stimulation and calcium mobilization by picosecond electric pulses

Semenov

Xiao

Kang

et al. 2015

Bioelectrochemistry

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We tested if picosecond electric pulses (psEP; 190 kV/cm, 500 ps at 50% height), which are much shorter than channel activation time, can activate voltage-gated (VG) channels. Cytosolic Ca2+ was monitored by Fura-2 ratiometric imaging in GH3 and NG108 cells (which express multiple types of VG calcium channels, VGCC), and in CHO cells (which express no VGCC). Trains of up to 100 psEP at 1 kHz elicited no response in CHO cells. However, even a single psEP significantly increased Ca2+ in both GH3 (by 114+/−48 nM) and NG108 cells (by 6 +/−1.1 nM). Trains of 100 psEP amplified the response to 379+/−33 nM and 719+/−315 nM, respectively. Ca2+ responses peaked within 2–15 s and recovered for over 100 s; they were 80–100% inhibited by verapamil and ω-conotoxin, but not by the substitution of Na+ with N-methyl-D-glucamine. There was no response to psEP in Ca2+-free medium, but adding external Ca2+ even 10 s later evoked Ca2+ response. We conclude that electrical stimuli as short as 500 ps can cause long-lasting opening of VGCC by a mechanism which does not involve conventional electroporation, heating (which was under 0.06 °K per psEP), or membrane depolarization by opening of VG Na+ channels.

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Frequency-dependent interaction of ultrashort E-fields with nociceptor membranes and proteins

Cited by 35 publications

References 55 publications

Nanosecond pulsed electric field thresholds for nanopore formation in neural cells

Nanosecond pulsed electric field thresholds for nanopore formation in neural cells

Enhanced Monitoring of Nanosecond Electric Pulse-Evoked Membrane Conductance Changes in Whole-Cell Patch Clamp Experiments

Cell stimulation and calcium mobilization by picosecond electric pulses

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