Open AccessTargeting Two-Pore-Domain Potassium Channels by Mechanical Stretch Instantaneously Modulates Action Potential Transmission in Mouse Sciatic Nerves
Author(s) -
Jia Liu,
Nishanth Ganeshbabu,
Noha Shalaby,
Longtu Chen,
Tiantian Guo,
Bin Feng
Publication year - 2021
Publication title -
acs chemical neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.158
H-Index - 69
ISSN - 1948-7193
DOI - 10.1021/acschemneuro.1c00052
Subject(s) - sciatic nerve , nerve conduction velocity , compound muscle action potential , biophysics , electrophysiology , chemistry , action potential , anatomy , materials science , neuroscience , biology
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.