Targeted disruption of Kir2.1 and Kir2.2 genes reveals the essential role of the inwardly rectifying K(+) current in K(+)-mediated vasodilation.
Targeted disruption of Kir2.1 and Kir2.2 genes reveals the essential role of the inwardly rectifying K(+) current in K(+)-mediated vasodilation.
复制标题
DOI：
10.1161/01.res.87.2.160
复制
发表时间：
2000-07
影响因子：
20.1
通讯作者：
J. Zaritsky;D. Eckman;G. Wellman;M. Nelson;T. Schwarz
中科院分区：
文献类型：
--
作者：
J. Zaritsky;D. Eckman;G. Wellman;M. Nelson;T. Schwarz
在缺乏Kir2.1和Kir2.2基因的小鼠脑动脉中检测了内向整流K（+）（Kir）电流和K（+）诱导的扩张的分子基础。证实了靶向等位基因纯合动物中完全不存在开放阅读框。Kir2.1（-/-）动物出生后8至12小时死亡，显然是由于继发性腭裂。相反，Kir2.2（-/-）动物是可行的和可繁殖的。在从对照新生动物分离的脑动脉肌细胞中观察到Kir电流，但在Kir2.1（-/-）动物的肌细胞中不存在。电压依赖性K（+）电流在新生儿对照和Kir2.1（-/-）动物的细胞中相似。细胞外K（+）浓度从6 mmol/L增加到15 mmol/L，可引起对照组和Kir2.2小鼠加压脑动脉中Ba（2+）敏感性扩张。相反，当细胞外K（+）浓度增加到15 mmol/L时，Kir2.1（-/-）动物的动脉没有扩张。总之，动脉平滑肌中Kir2.1基因的表达是脑动脉中Kir电流和K（+）诱导的扩张所必需的。
The molecular bases of inwardly rectifying K(+) (Kir) currents and K(+)-induced dilations were examined in cerebral arteries of mice that lack the Kir2.1 and Kir2.2 genes. The complete absence of the open reading frame in animals homozygous for the targeted allele was confirmed. Kir2.1(-/-) animals die 8 to 12 hours after birth, apparently due to a complete cleft of the secondary palate. In contrast, Kir2.2(-/-) animals are viable and fertile. Kir currents were observed in cerebral artery myocytes isolated from control neonatal animals but were absent in myocytes from Kir2.1(-/-) animals. Voltage-dependent K(+) currents were similar in cells from neonatal control and Kir2.1(-/-) animals. An increase in the extracellular K(+) concentration from 6 to 15 mmol/L caused Ba(2+)-sensitive dilations in pressurized cerebral arteries from control and Kir2.2 mice. In contrast, arteries from Kir2.1(-/-) animals did not dilate when the extracellular K(+) concentration was increased to 15 mmol/L. In summary, Kir2.1 gene expression in arterial smooth muscle is required for Kir currents and K(+)-induced dilations in cerebral arteries.