Deletion of Kir6.2/SUR1 potassium channels rescues diminishing of DA neurons via decreasing iron accumulation in PD

Molecular and Cellular Neurosciences
Qian ZhangGang Hu

Abstract

ATP-sensitive potassium (K-ATP) channels express in the central nervous system extensively which coupling cell metabolism and cellular electrical activity. K-ATP channels in mature substantia nigra (SN) dopaminergic (DA) neurons are composed of inwardly rectifying potassium channel (Kir) subunit 6.2 and sulfonylurea receptor 1 (SUR1). Our previous study revealed that regulating K-ATP channel exerts the protective effect on DA neurons in a mouse model of Parkinson's disease (PD). However, the detailed mechanism underlying the role of Kir6.2/K-ATP remains unclear. In the present study, we found the deletion of Kir6.2 dramatically alleviated PD-like motor dysfunction of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) PD model. We further found that Kir6.2 knockout selectively restored the reduction of both DA neuronal number and dopamine transmitter level in the nigrostriatal of MPTP-treated PD mice. To gain some understanding on the molecular basis of this effect, we focused on the regulation of Kir6.2 deletion on iron metabolism which is tightly associated with DA neuron damage. We found that Kir6.2 knockout suppressed the excessive iron accumulation in MPTP-treated mouse midbrain and inhibited the upregulation of ferritin l...Continue Reading

Citations

Jan 15, 2020·NPJ Parkinson's Disease·James P HarrisD Kacy Cullen
Jan 13, 2021·Brain Research Bulletin·Sha ZhaoZeGang Ma
Feb 16, 2021·The Journal of International Medical Research·Meng-Yu LiuLin Ma
Jan 8, 2021·NPJ Parkinson's Disease·James P HarrisD Kacy Cullen
Aug 13, 2021·Neural Regeneration Research·Iván Alquisiras-BurgosPenélope Aguilera

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