摘要：SummaryGlucose-responsive ATP-sensitive potassium channels (KATP) 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 KATPin the peripheral nervous system (PNS) are poorly understood. Here, we determine the roles of KATPin the PNS using KATP-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. KATPsubunits were expressed in mouse DRG, and expression of certain subunits including Kir6.2 was increased in diabetic mice. InKir6.2-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, KATPmay contribute to the development of peripheral neuropathy.Graphical abstractDisplay OmittedHighlights•Transcript levels of KATPchannels in DRG neurons increase in diabetic mice•KATPchannel inhibition shortens but its activation elongates neurites of DRG neurons•Kir6.2−/−mice present the dysfunction in the peripheral nerves•Kir6.2−/−mice present ultrastructural abnormalities in peripheral sensory nervesMolecular neuroscience; Cellular neuroscience; Sensory neuroscience
