Kir6.2-deficient mice develop somatosensory dysfunction and axonal loss in the peripheral nerves

Hiromi Nakai-Shimoda, Tatsuhito Himeno, Tetsuji Okawa, Emiri Miura-Yura, Sachiko Sasajima, Makoto Kato, Yuichiro Yamada, Yoshiaki Morishita, Shin Tsunekawa, Yoshiro Kato, Yusuke Seino, Rieko Inoue, Masaki Kondo, Susumu Seino, Keiko Naruse, Koichi Kato, Hiroki Mizukami, Jiro Nakamura, Hideki Kamiya

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4 Citations (Scopus)

Abstract

Glucose-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 KATP in the peripheral nervous system (PNS) are poorly understood. Here, we determine the roles of KATP in 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. KATP 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, KATP may contribute to the development of peripheral neuropathy.

Original languageEnglish
Article number103609
JournaliScience
Volume25
Issue number1
DOIs
Publication statusPublished - 21-01-2022

All Science Journal Classification (ASJC) codes

  • General

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