The Protective Roles And Mechanisms Of Novel ATP-sensitive Potassium Channel Opener Iptakalim On MPP～+ Model Rats Of Parkinson's Disease

Parkinson's disease (PD) is a progressive, age-associated, neurodegenerative disease characterized by bradykinesia, resting tremor, tigidity and gait disturbance. The pathological hallmarks and biochemical changes of PD are the loss of nigrostriatal dopaminergic neurons, the reduction of dopamine (DA) content in the striatum and the presence of intraneuronal proteinacious cytoplasmic inclusions, termed "Lewy Bodies". Up till now, its etiology remains unclear to date. Various mechanisms, including mitochondrial defects, oxidative stress, glutamate toxicity, genetic factors and apoptosis, may be involved in the pathogenesis of PD. Therapeutic strategies derived from these, such as L-DOPA administration, are essentially symptomatical or accompanied with serious side' effects, and cannot stop the progressive loss of dopaminergic neurons. Hence, many studies are focused on searching for new potential therapeutic targets and agents for the treatment of PD. Emerging evidences, including from our laboratory, has revealed that ATP-sensitive potassium (K_ATP) channels play dominant protective roles on several PD models in vivo and in vitro.K_ATP channels, originally discovered in heart, are widely distributed in many tissues and cell types. They couple the metabolic state of the cell to membrane potential by sensing changes in intracellular adenine nucleotide concentration. K_ATP channels are thought to play important...