Targeting Two-Pore-Domain Potassium Channels by Mechanical Stretch Instantaneously Modulates Action Potential Transmission in Mouse Sciatic Nerves
| Autor: | Noha Shalaby, Longtu Chen, Tiantian Guo, Jia Liu, Bin Feng, Nishanth Ganeshbabu |
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| Rok vydání: | 2021 |
| Předmět: |
Agonist
Ruthenium red Physiology medicine.drug_class Cognitive Neuroscience Neural Conduction Action Potentials Nerve Fibers Myelinated Biochemistry Article Nerve conduction velocity Mice chemistry.chemical_compound Neuromodulation medicine Animals Chemistry Cell Biology General Medicine Sciatic Nerve Axons Potassium channel Peripheral medicine.anatomical_structure Biophysics Mechanosensitive channels Sciatic nerve |
| Zdroj: | ACS Chem Neurosci |
| ISSN: | 1948-7193 |
| Popis: | Recent reports indicate dominant roles of TRAAK and TREK-1 channels, i.e., mechanosensitive two-pore-domain potassium channels (K2P) at the nodes of Ranvier for action potential repolarization in mammalian peripheral nerves. Functional changes in mammalian peripheral nerve conduction by mechanical stretch studied by recording compound action potentials lack the necessary resolution to detect subtle neuromodulatory effects on conduction velocity. In this study, we developed a novel in vitro approach that enables single-fiber recordings from individual mouse sciatic nerve axons while delivering computer-controlled stepped stretch to the sciatic nerve trunk. Axial stretch instantaneously increased the conduction delay in both myelinated A-fibers and unmyelinated C-fibers. Increases in conduction delay linearly correlated with increases in axial stretch ratio for both A- and C-fibers. The slope of the increase in conduction delay versus stretch ratio was steeper in C-fibers than in A-fibers. Moderate axial stretch (14-19% of in vitro length) reversibly blocked 37.5% of unmyelinated C-fibers but none of the eight myelinated A-fibers tested. Application of arachidonic acid, an agonist to TRAAK and TREK-1 to sciatic nerve trunk, blocks axonal transmission in both A- and C-fibers with delayed onset and prolonged block. Also, the application of an antagonist ruthenium red showed a tendency of suppressing the stretch-evoked increase in conduction delay. These results could draw focused research on pharmacological and mechanical activation of K2P channels as a novel neuromodulatory strategy to achieve peripheral nerve block. |
| Databáze: | OpenAIRE |
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