Modulation of the molecular composition of large conductance, Ca2+activated K+ channels in vascular smooth muscle during hypertension
Modulation of the molecular composition of large conductance, Ca2+activated K+ channels in vascular smooth muscle during hypertension
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DOI：
10.1172/jc1200318684
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发表时间：
2003-09-01
影响因子：
15.9
通讯作者：
Santana, LF
中科院分区：
文献类型：
--
作者：
Amberg, GC;Bonev, AD;Santana, LF
高血压是一种以血管张力增高为特征的临床综合征。然而，在获得性高血压血管功能障碍的分子机制仍然没有得到解决。肌浆网中通过兰尼碱受体（Ca 2+火花）的局部细胞内Ca 2+释放事件与大电导Ca 2+激活的K+（BK）通道的激活密切相关，以提供对抗血管收缩的超极化影响。在这项研究中，我们测试的假设，减少钙火花-BK通道耦合的基础血管平滑肌功能障碍，在获得性高血压。我们发现，在高血压中，β 1亚基的表达相对于BK通道的孔形成亚基减少。因此，BK通道在功能上与Ca 2+火花解偶联。与此一致，BK通道对血管张力的贡献在高血压期间减少。我们的结论是，BK通道β 1亚基的下调有助于高血压血管功能障碍。这些结果支持BK通道亚基组成的变化调节动脉平滑肌功能的新概念。
Hypertension is a clinical syndrome characterized by increased vascular tone. However, the molecular mechanisms underlying vascular dysfunction during acquired hypertension remain unresolved. Localized intracellular Ca2+ release events through ryanodine receptors (Ca2+ sparks) in the sarcoplasmic reticulum are tightly coupled to the activation of large-conductance, Ca2+-activated K+ (BK) channels to provide a hyperpolarizing influence that opposes vasoconstriction. In this study we tested the hypothesis that a reduction in Ca2+ spark-BK channel coupling underlies vascular smooth muscle dysfunction during acquired hypertension. We found that in hypertension, expression of the beta1 subunit was decreased relative to the pore-forming a subunit of the BK channel. Consequently, the BK channels were functionally uncoupled from Ca2+ sparks. Consistent with this, the contribution of BK channels to vascular tone was reduced during hypertension. We conclude that downregulation of the beta1 subunit of the BK channel contributes to vascular dysfunction in hypertension. These results support the novel concept that changes in BK channel subunit composition regulate arterial smooth muscle function.