ABSTRACT
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 K7/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.
Subject(s)
Animals , Humans , Parkinson Disease , Metabolism , Potassium Channels , MetabolismABSTRACT
Aim To explore the effect of activated SK channels(small conductance Ca2+-activated K+ channels) on morphine-induced hyperalgesia in the spinal cord in mice.Methods Adult C57BL6/N male mice were chosen to establish the model of morphine-hyperalgesia.The changes of tail withdrawal latency(TWL), mechanical withdrawal threshold(MWT) and the threshold of visceral pain were observed after intrathecal 1-EBIO, the agonist of SK channels.Results Compared with the control group, TWL, MWT and the threshold of visceral pain were decreased after morphine injection.After intrathecal 1-EBIO, the TWL, MWT and visceral pain threshold were increased.The level of spinal membrane SK2 expression in morphine-treated mice was decreased compared with that of control group.After intrathecal 1-EBIO, the level of spinal membrane SK2 expression was increased.Conclusion SK channels in the spinal cord are involved in morphine-induced hyperalgesia in mice.
ABSTRACT
Small conductance Ca 2+ activated potassium channels ( SK channels) are potassium selective , voltage independent, and Ca 2+ high sensitivity. SK channels are widely distributed in neurons. SK underlie the slow afterhyperpolarization , which regulate the fire of neurons by spike frequency adaptation. Three mammalian SK channels (SK 1, SK 2, SK 3) have been cloned . Ca 2+ , CaM and neurotransimitters involve in the gating of these channels. The changes of these channels may result in memory, neuromuscular disorder and schizophrenia.