-deficient mice develop somatosensory dysfunction and axonal loss in the peripheral nerves.

Glucose-responsive ATP-sensitive potassium channels (K) 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 in the peripheral nervous system (PNS) are poorly understood. Here, we determine the roles of K in the PNS using K-deficient (-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 subunits were expressed in mouse DRG, and expression of certain subunits including Kir6.2 was increased in diabetic mice. In -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 may contribute to the development of peripheral neuropathy.