Potassium Channels: A Potential Therapeutic Target for Parkinson's Disease

The pathogenesis of the second major neurodegenerative disorder, Parkinson's disease (PD), is closely associated with the dysfunction of potassium (K⁺) channels. Therefore, PD is also considered to be an ion channel disease or neuronal channelopathy. Mounting evidence has shown that K⁺ channels play crucial roles in the regulations of neurotransmitter release, neuronal excitability, and cell volume. Inhibition of K⁺ channels enhances the spontaneous firing frequency of nigral dopamine (DA) neurons, induces a transition from tonic firing to burst discharge, and promotes the release of DA in the striatum. Recently, three K⁺ channels have been identified to protect DA neurons and to improve the motor and non-motor symptoms in PD animal models: small conductance (SK) channels, A-type K⁺ channels, and K_V7/KCNQ channels. In this review, we summarize the physiological and pharmacological effects of the three K⁺ channels. We also describe in detail the laboratory investigations regarding K⁺ channels as a potential therapeutic target for PD.