Dual effect of NO on KATP+ current of mouse pancreatic B-cells:: stimulation by deenergizing mitochondria and inhibition by direct interaction with the channel
Dual effect of NO on KATP+ current of mouse pancreatic B-cells:: stimulation by deenergizing mitochondria and inhibition by direct interaction with the channel
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DOI：
10.1016/s0005-2736(99)00242-4
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发表时间：
2000-03-15
影响因子：
3.4
通讯作者：
Krippeit-Drews, P
中科院分区：
文献类型：
--
作者：
Drews, G;Krämer, C;Krippeit-Drews, P
一氧化氮(NO)被认为是I型糖尿病(IDDM)B细胞功能受损的原因之一。在代谢完整的小鼠B细胞上，真NO(20mM)引起K-ATP(+)电流的双相效应，即一过性增加和连续的几乎完全抑制。这与我们以前观察到的NO供体S-亚硝半胱氨酸(SNOC，1 mM)的作用非常相似，这表明仅仅是NO引起了这种效应的两个阶段。我们现在证明，电流幅度的增加伴随着线粒体膜电位Delta Psi的去极化和伴随而来的ATP/ADP比率的降低。因此，电流幅度的增加可能是由于NO对细胞新陈代谢的干扰。随后K-ATP(+)电流的抑制被认为是由对通道的直接作用引起的，因为在切除的斑块中测得的K-ATP(+)单通道电流活动被真实的NO和SNOC强烈地降低。我们的数据揭示了NO对胰腺B细胞K-ATP(+)通道双相作用的新机制。(C)2000 Elsevier Science B.V.保留所有权利。
Nitric oxide (NO) is assumed to contribute to the impairment of B-cell function in type I diabetes mellitus (IDDM). In the present paper we show that in mouse B-cells with intact metabolism authentic NO (20 mu M) led to a biphasic effect on the K-ATP(+) current, namely a transient increase and a consecutive almost complete inhibition. This resembles closely the effect that we have observed previously with the NO donor S-nitrosocysteine (SNOC, 1 mM) suggesting that merely NO caused both phases of this effect. We now demonstrate that the rise in the current amplitude was accompanied by a depolarization of the mitochondrial membrane potential Delta Psi and a concomitant reduction in the ATP/ADP ratio. Thus, it seems likely that the increase in current amplitude is due to the interference of NO With cell metabolism. The subsequent inhibition of the K-ATP(+) current is assumed to be caused by a direct effect on the channel since K-ATP(+) single channel current activity measured in excised patches was strongly reduced by authentic NO and SNOC. Our data reveal new insights into the mechanisms underlying the biphasic action of NO on K-ATP(+), channels in pancreatic B-cells. (C) 2000 Elsevier Science B.V. All rights reserved.