NITRIC-OXIDE DIRECTLY ACTIVATES CALCIUM-DEPENDENT POTASSIUM CHANNELS IN VASCULAR SMOOTH-MUSCLE
NITRIC-OXIDE DIRECTLY ACTIVATES CALCIUM-DEPENDENT POTASSIUM CHANNELS IN VASCULAR SMOOTH-MUSCLE
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DOI：
10.1038/368850a0
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发表时间：
1994-04-28
期刊：
影响因子：
64.8
通讯作者：
COHEN, RA
中科院分区：
文献类型：
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作者：
BOLOTINA, VM;NAJIBI, S;COHEN, RA
一氧化氮是主要的内皮衍生的放松因子（EDRF）（1-3），被认为通过刺激鸟苷酸环化酶的积累，其产物环状GMP的积累和CGMP依赖性修饰的几种细胞内过程来放松平滑肌细胞。 （4-5），包括通过CGMP依赖性蛋白激酶激活钾通道（6,7）。在这里，我们提供的证据表明，外源一氧化氮和天然EDRF都可以直接激活无细胞膜片中的单个Ca2+依赖性K+通道（K-CA（+）），而无需CGMP。在甲基蓝蓝色抑制鸟甘酸环化酶时，兔主动脉对一氧化氮的相当大松弛被持续存在，这被Charybdotoxin（charybdotoxin）阻塞，Charybdotoxin是K-CA（+）通道的一种特异性抑制剂。这些研究表明，一氧化氮在K-CA（+）通道上的直接作用。
NITRIC oxide is the major endothelium-derived relaxing factor (EDRF)(1-3), and it is thought to relax smooth muscle cells by stimulation of guanylate cyclase, accumulation of its product cyclic GMP, and cGMP-dependent modification of several intracellular processes(4-5), including activation of potassium channels through cGMP-dependent protein kinase(6,7). Here we present evidence that both exogenous nitric oxide and native EDRF can directly activate single Ca2+-dependent K+ channels (K-Ca(+)) in cell-free membrane patches without requiring cGMP. Under conditions when guanylate cyclase was inhibited by methylene blue, considerable relaxation of rabbit aorta to nitric oxide persisted which was blocked by charybdotoxin, a specific inhibitor of K-Ca(+) channels. These studies demonstrate a novel direct action of nitric oxide on K-Ca(+) channels.