黑质
致密部
化学
多巴胺
钾通道
药理学
生物物理学
神经科学
鱼藤酮
多巴胺能
神经保护
钾通道阻滞剂
生物
线粒体
生物化学
作者
Wu Chen,Kechun Yang,Qiang Liu,Matoko Wakui,Guo Jin,Xuechu Zhen,Jie Wu
标识
DOI:10.1016/j.neuropharm.2010.08.018
摘要
Tetrahydroberberine (THB) exhibits neuroprotective effects but its targets and underlying mechanisms are largely unknown. Emerging evidence indicates that ATP-sensitive potassium (KATP) channels in the substantia nigra pars compacta (SNc) promote Parkinson disease (PD) pathogenesis, thus blocking KATP channels may protect neurons against neuronal degeneration. In the present study, we tested a hypothesis that THB blocks KATP channels in dopaminergic (DA) neurons acutely dissociated from rat SNc. Using perforated patch-clamp recording in current-clamp mode, the functional KATP channels can be opened by persistent perfusion of rotenone, an inhibitor of complex I of the mitochondrial respiratory chain. Bath-application of THB reversibly blocks opened KATP channels in a concentration-dependent manner, which is comparable to a classical KATP channel blocker, Tol. Compared to THB analogs, l-stepholidine (l-SPD) or l-tetrahydropalmatine (l-THP), THB exhibits more profound blockade in KATP channels. In addition, exposure of THB alone to the recorded neuron increases action potential firing, and THB also restores rotenone-induced membrane hyperpolarization in the presence of dopamine D2 receptor antagonist (sulpiride), suggesting that THB exhibits an excitatory effect on SNc DA neurons through the block of KATP channels. Collectively, the blockade of neuronal KATP channels by THB in SNc DA neurons is a novel pharmacological mechanism of THB, which may contribute to its neuroprotective effects in PD.
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