TY - JOUR
T1 - Kir6.2-deficient mice develop somatosensory dysfunction and axonal loss in the peripheral nerves
AU - Nakai-Shimoda, Hiromi
AU - Himeno, Tatsuhito
AU - Okawa, Tetsuji
AU - Miura-Yura, Emiri
AU - Sasajima, Sachiko
AU - Kato, Makoto
AU - Yamada, Yuichiro
AU - Morishita, Yoshiaki
AU - Tsunekawa, Shin
AU - Kato, Yoshiro
AU - Seino, Yusuke
AU - Inoue, Rieko
AU - Kondo, Masaki
AU - Seino, Susumu
AU - Naruse, Keiko
AU - Kato, Koichi
AU - Mizukami, Hiroki
AU - Nakamura, Jiro
AU - Kamiya, Hideki
N1 - Publisher Copyright:
© 2021 The Author(s)
PY - 2022/1/21
Y1 - 2022/1/21
N2 - 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.
AB - 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.
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U2 - 10.1016/j.isci.2021.103609
DO - 10.1016/j.isci.2021.103609
M3 - Article
AN - SCOPUS:85121574451
SN - 2589-0042
VL - 25
JO - iScience
JF - iScience
IS - 1
M1 - 103609
ER -
