Bolotina V M, Najibi S, Palacino J J, Pagano P J, Cohen R A
Robert Dawson Evans Department of Clinical Research, Boston University Medical Center, Massachusetts 02118.
Nature. 1994 Apr 28;368(6474):850-3. doi: 10.1038/368850a0.
Nitric oxide is the major endothelium-derived relaxing factor (EDRF), 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, including activation of potassium channels through cGMP-dependent protein kinase. Here we present evidence that both exogenous nitric oxide and native EDRF can directly activate single Ca(2+)-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.
一氧化氮是主要的内皮源性舒张因子（EDRF），人们认为它通过刺激鸟苷酸环化酶、其产物环磷酸鸟苷（cGMP）的积累以及cGMP依赖性修饰多种细胞内过程（包括通过cGMP依赖性蛋白激酶激活钾通道）来舒张平滑肌细胞。在此我们提供证据表明，外源性一氧化氮和内源性EDRF均可在无细胞的膜片上直接激活单个钙依赖性钾通道（K+Ca），而无需cGMP。在鸟苷酸环化酶被亚甲蓝抑制的条件下，兔主动脉对一氧化氮仍有相当程度的舒张，这种舒张被K+Ca通道的特异性抑制剂蝎毒素所阻断。这些研究证明了一氧化氮对K+Ca通道的一种新的直接作用。
