Kilohertz waveforms optimized to produce closed-state Na+ channel inactivation eliminate onset response in nerve conduction block.
The delivery of kilohertz frequency alternating current (KHFAC) generates rapid, controlled, and reversible conduction block in motor, sensory, and autonomic nerves, but causes transient activation of action potentials at the onset of the blocking current. We implemented a novel engineering optimiza...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-06-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1007766 |
| _version_ | 1818582261134524416 |
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| author | Guosheng Yi Warren M Grill |
| author_facet | Guosheng Yi Warren M Grill |
| author_sort | Guosheng Yi |
| collection | DOAJ |
| description | The delivery of kilohertz frequency alternating current (KHFAC) generates rapid, controlled, and reversible conduction block in motor, sensory, and autonomic nerves, but causes transient activation of action potentials at the onset of the blocking current. We implemented a novel engineering optimization approach to design blocking waveforms that eliminated the onset response by moving voltage-gated Na+ channels (VGSCs) to closed-state inactivation (CSI) without first opening. We used computational models and particle swarm optimization (PSO) to design a charge-balanced 10 kHz biphasic current waveform that produced conduction block without onset firing in peripheral axons at specific locations and with specific diameters. The results indicate that it is possible to achieve onset-free KHFAC nerve block by causing CSI of VGSCs. Our novel approach for designing blocking waveforms and the resulting waveform may have utility in clinical applications of conduction block of peripheral nerve hyperactivity, for example in pain and spasticity. |
| first_indexed | 2024-12-16T07:46:34Z |
| format | Article |
| id | doaj.art-a3694850014b4016981a415b00798801 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-16T07:46:34Z |
| publishDate | 2020-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-a3694850014b4016981a415b007988012022-12-21T22:38:57ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582020-06-01166e100776610.1371/journal.pcbi.1007766Kilohertz waveforms optimized to produce closed-state Na+ channel inactivation eliminate onset response in nerve conduction block.Guosheng YiWarren M GrillThe delivery of kilohertz frequency alternating current (KHFAC) generates rapid, controlled, and reversible conduction block in motor, sensory, and autonomic nerves, but causes transient activation of action potentials at the onset of the blocking current. We implemented a novel engineering optimization approach to design blocking waveforms that eliminated the onset response by moving voltage-gated Na+ channels (VGSCs) to closed-state inactivation (CSI) without first opening. We used computational models and particle swarm optimization (PSO) to design a charge-balanced 10 kHz biphasic current waveform that produced conduction block without onset firing in peripheral axons at specific locations and with specific diameters. The results indicate that it is possible to achieve onset-free KHFAC nerve block by causing CSI of VGSCs. Our novel approach for designing blocking waveforms and the resulting waveform may have utility in clinical applications of conduction block of peripheral nerve hyperactivity, for example in pain and spasticity.https://doi.org/10.1371/journal.pcbi.1007766 |
| spellingShingle | Guosheng Yi Warren M Grill Kilohertz waveforms optimized to produce closed-state Na+ channel inactivation eliminate onset response in nerve conduction block. PLoS Computational Biology |
| title | Kilohertz waveforms optimized to produce closed-state Na+ channel inactivation eliminate onset response in nerve conduction block. |
| title_full | Kilohertz waveforms optimized to produce closed-state Na+ channel inactivation eliminate onset response in nerve conduction block. |
| title_fullStr | Kilohertz waveforms optimized to produce closed-state Na+ channel inactivation eliminate onset response in nerve conduction block. |
| title_full_unstemmed | Kilohertz waveforms optimized to produce closed-state Na+ channel inactivation eliminate onset response in nerve conduction block. |
| title_short | Kilohertz waveforms optimized to produce closed-state Na+ channel inactivation eliminate onset response in nerve conduction block. |
| title_sort | kilohertz waveforms optimized to produce closed state na channel inactivation eliminate onset response in nerve conduction block |
| url | https://doi.org/10.1371/journal.pcbi.1007766 |
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