ATP-sensitive potassium channels: A double-edged sword in neurodegenerative diseases

ATP-sensitive potassium channels (K_ATP channels), a group of vital channels that link the electrical activity of the cell membrane with cell metabolism, were discovered on the ventricular myocytes of guinea pigs by Noma using the patch-clamp technique in 1983. Subsequently, K_ATP channels have been found to be expressed in pancreatic β cells, cardiomyocytes, skeletal muscle cells, and nerve cells in the substantia nigra (SN), hippocampus, cortex, and basal ganglia. K_ATP channel openers (KCOs) diazoxide, nicorandil, minoxidil, and the K_ATP channel inhibitor glibenclamide have been shown to have anti-hypertensive, anti-myocardial ischemia, and insulin-releasing regulatory effects. Increasing evidence has suggested that K_ATP channels also play roles in Alzheimer's disease (AD), Parkinson's disease (PD), vascular dementia (VD), Huntington's disease (HD) and other neurodegenerative diseases. KCOs and K_ATP channel inhibitors protect neurons from injury by regulating neuronal excitability and neurotransmitter release, inhibiting abnormal protein aggregation and Ca²⁺ overload, reducing reactive oxygen species (ROS) production and microglia activation. However, K_ATP channels have dual effects in some cases. In this review, we focus on the roles of K_ATP channels and their related openers and inhibitors in neurodegenerative diseases. This will enable us to precisely take advantage of the K_ATP channels and provide new ideas for the treatment of neurodegenerative diseases.