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Kir6.2-deficient mice develop somatosensory dysfunction and axonal loss in the peripheral nerves
Glucose-responsive ATP-sensitive potassium channels (K(ATP)) are expressed in a variety of tissues including nervous systems. The depolarization of the membrane potential induced by glucose may lead to hyperexcitability of neurons and induce excitotoxicity. However, the roles of K(ATP) in the periph...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8719014/ https://www.ncbi.nlm.nih.gov/pubmed/35005553 http://dx.doi.org/10.1016/j.isci.2021.103609 |
Sumario: | Glucose-responsive ATP-sensitive potassium channels (K(ATP)) are expressed in a variety of tissues including nervous systems. The depolarization of the membrane potential induced by glucose may lead to hyperexcitability of neurons and induce excitotoxicity. However, the roles of K(ATP) in the peripheral nervous system (PNS) are poorly understood. Here, we determine the roles of K(ATP) in the PNS using K(ATP)-deficient (Kir6.2-deficient) mice. We demonstrate that neurite outgrowth of dorsal root ganglion (DRG) neurons was reduced by channel closers sulfonylureas. However, a channel opener diazoxide elongated the neurite. K(ATP) subunits were expressed in mouse DRG, and expression of certain subunits including Kir6.2 was increased in diabetic mice. In Kir6.2-deficient mice, the current perception threshold, thermal perception threshold, and sensory nerve conduction velocity were impaired. Electron microscopy revealed a reduction of unmyelinated and small myelinated fibers in the sural nerves. In conclusion, K(ATP) may contribute to the development of peripheral neuropathy. |
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