ZD7288 是否为超极化激活环核苷酸门控通道电流的选择性阻断剂？
Is ZD7288 a selective blocker of hyperpolarization-activated cyclic nucleotide-gated channel currents?
机构信息
Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Wuhan, China.
出版信息
Channels (Austin). 2012 Nov-Dec;6(6):438-42. doi: 10.4161/chan.22209. Epub 2012 Sep 18.
Abstract
ZD7288 has been widely used as a tool in the study of hyperpolarization-activated cyclic nucleotide-gated channels (HCN channels), and to test the relationships between HCN channels and heart and brain function. ZD7288 is widely considered a selective blocker of HCN currents. Here we show that ZD7288 inhibits not only HCN channel currents, but also Na(+) currents in DRG neurons and ZD7288 was confirmed to inhibit Na(+) current in HEK293 cells transfected with Na(v)1.4 plasmids. Thus our findings challenge the view that ZD7288 is a selective blocker of HCN channels. Conclusions about the role of NCN channels in neuronal function should be re-evaluated if based exclusively on the effect of ZD7288.
摘要
ZD7288 已被广泛用作研究超极化激活环核苷酸门控通道（HCN 通道）的工具，并用于测试 HCN 通道与心脏和大脑功能之间的关系。ZD7288 被广泛认为是 HCN 电流的选择性阻断剂。在这里，我们表明 ZD7288 不仅抑制 HCN 通道电流，还抑制 DRG 神经元中的钠离子电流，并且在转染 Na(v)1.4 质粒的 HEK293 细胞中证实 ZD7288 抑制钠离子电流。因此，我们的发现挑战了 ZD7288 是 HCN 通道选择性阻断剂的观点。如果基于 ZD7288 的作用来评估 NCN 通道在神经元功能中的作用，那么应该重新评估。
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2
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3
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4
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5
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6
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7
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8
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9
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10
Voltage-clamp analysis of muscarinic excitation in hippocampal neurons.海马神经元毒蕈碱样兴奋的电压钳分析
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