Dynamic Regulation of the Subunit Composition of BK Channels in Smooth Muscle.
Dynamic Regulation of the Subunit Composition of BK Channels in Smooth Muscle.
复制标题
平滑肌 BK 通道亚基组成的动态调节。
DOI：
10.1161/circresaha.117.311723
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发表时间：
2017
影响因子：
20.1
通讯作者：
Tune,JohnathanD
中科院分区：
文献类型：
--
作者：
Dick,GregoryM;Tune,JohnathanD
Dick和Tune小GTP酶调节大K595，特别是关于β1亚单位，以前在其他动脉中已有文献报道。例如，尽管来自脑动脉和提肌主动脉的平滑肌细胞具有相似的BK通道电流密度，但来自提肌主动脉的肌细胞中的β1：α比率降低。8、9此外，令人惊讶的是，α亚单位蛋白在脑动脉中的表达比在提睾肌中的≈高20倍。此外，与冠状循环相比，BK通道似乎是大脑床上更重要的音调调节器。具体地说，尽管BK通道调节脑血流的代谢控制，11它们似乎对冠状动脉血流的代谢调节几乎没有影响(如果有的话)。12然而，冠状动脉血管BK通道有助于多种激动剂的血管扩张反应，例如，内皮依赖性扩张剂，如缓激肽。13这些发现表明，在不同血管床的平滑肌细胞中，BK通道是如何调节的，以及它们是如何发挥作用的，存在着一些非常根本的差异。此外，值得注意的是，Zhai等人的实验是在大脑动脉中进行的，大脑动脉的行为与负责血流调节的小动脉非常不同；因此，知识中的一个重要缺口涉及如何将这些概念应用于微循环。此外，鉴于BK通道功能和亚基组成在高血压14和肥胖/2型糖尿病等疾病状态下发生改变，15这种新的膜转运机制值得进一步深入研究，因为它可能与一些关键的病理特征有关。
Dick and Tune Small GTPase Regulates Big K 595 particularly with regard to the β1 subunit, have been documented previously in other arteries. For example, although smooth muscle cells from cerebral and cremaster arteries have similar BK channel current densities, there is a reduced β1: α ratio in myocytes from cremaster arteries. 8, 9 Moreover, it is very surprising that expression of the α subunit protein in cerebral arteries is≈ 20× higher than in cremaster. 10 Further, it seems that BK channels are more important regulators of tone in the cerebral bed compared with, for example, the coronary circulation. Specifically, although BK channels regulate metabolic control of cerebral blood flow, 11 they seem to have little, if any, impact on metabolic regulation of coronary blood flow. 12 However, coronary vascular BK channels contribute to vasodilator responses to multiple agonists, for example, endothelium-dependent dilators such as bradykinin. 13 These findings suggest that there are some very fundamental differences in how BK channels are regulated and how they function in the smooth muscle cells of various vascular beds. Further, it is noted that the experiments by Zhai et al4 were performed in cerebral arteries which can act quite differently than arterioles responsible for flow regulation; therefore, an important gap in knowledge deals with how these concepts apply to the microcirculation. Furthermore, given that BK channel function and subunit composition are altered in diseases states such as hypertension14 and obesity/type 2 diabetes mellitus, 15 this novel membrane trafficking mechanism merits intense future investigation, as it may be responsible for some key features of pathology.