• Neuroscience · Sep 2021

    L5-6 spinal nerve ligation-induced neuropathy changes the location and function of Ca2+ channels and Cdk5 and affects the compound action potential in adjacent intact L4 afferent fibers.

    • Kimberly Gomez, Alberto Vargas-Parada, Paz Duran, Alejandro Sandoval, Rodolfo Delgado-Lezama, Rajesh Khanna, and Ricardo Felix.
    • Department of Physiology, Biophysics and Neuroscience, Centre for Research and Advanced Studies (Cinvestav), Mexico City, Mexico.
    • Neuroscience. 2021 Sep 1; 471: 203120-31.

    AbstractVoltage-gated Ca2+ (CaV) channels regulate multiple cell processes, including neurotransmitter release, and have been associated with several pathological conditions, such as neuropathic pain. Cdk5, a neuron-specific kinase, may phosphorylate CaV channels, altering their functional expression. During peripheral nerve injury, upregulation of CaV channels and Cdk5 in the dorsal root ganglia (DRG) and the spinal cord, has been correlated with allodynia. We recently reported an increase in the amplitude of the C component of the compound action potential (cAP) of afferent fibers in animals with allodynia induced by L5-6 spinal nerve ligation (SNL), recorded in the corresponding dorsal roots. This was related to an increase in T-type (CaV3.2) channels generated by Cdk5-mediated phosphorylation. Here, we show that CaV channel functional expression is also altered in the L4 adjacent intact afferent fibers in rats with allodynia induced by L5-6 SNL. Western blot analysis showed that both Cdk5 and CaV3.2 total levels are not increased in the DRG L3-4, but their subcellular distribution changes by concentrating on the neuronal soma. Likewise, the Cdk5 inhibitor olomoucine affected the rapid and the slow C components of the cAP recorded in the dorsal roots. Patch-clamp recordings revealed an increase in T- and N-type currents recorded in the soma of acute isolated L3-4 sensory neurons after L5-6 SNL, which was prevented by olomoucine. These findings suggest changes in CaV channels location and function in L3-4 afferent fibers associated with Cdk5-mediated phosphorylation after L5-6 SNL, which may contribute to nerve injury-induced allodynia.Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.

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