Cheng Jun, Mao Liang, Wen Jing, Li Peng-Yun, Wang Na, Tan Xiao-Qiu, Zhang Xiao-Dong, Zeng Xiao-Rong, Xu Liang, Xia Xian-Ming, Xia Dong, He Kai, Su Song, Yao Hui, Yang Yan
Key Laboratory of Medical Electrophysiology of Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, China.
The First Affiliated Hospital, Southwest Medical University, Luzhou, China.
J Am Heart Assoc. 2016 Sep 14;5(9):e003913. doi: 10.1161/JAHA.116.003913.
Large-conductance calcium- and voltage-activated potassium channels (BKC a channels) play important roles in the maintenance of vascular tone, and their dysregulation is associated with abnormal vascular relaxation and contraction. We tested the changes in BKC a channel properties in patients at different ages to assess the effects of hypertension and aging on the functional changes of BKC a channels.
Patch clamp was performed to detect the activities of BKC a channels in freshly isolated human mesenteric artery smooth muscle cells from younger patients (aged ≤45 years) without hypertension, older patients (aged ≥65 years) without hypertension, and older patients with hypertension. The expression of mRNA and protein from BKC a channels was evaluated by reverse transcription polymerase chain reaction and Western blot analysis, respectively. Results showed that the whole-cell current density, spontaneous transient outward current, and Ca(2+) sensitivity of the artery smooth muscle cells were significantly decreased in the older patients with hypertension; the decreases were insignificant in the older patients without hypertension, although a clear tendency to have spontaneous transient outward current was detected in these patients. The expression of both mRNA and protein of BKC a subunits α and β1 was significantly decreased in the older patients with hypertension but not in the older patients without hypertension compared with the younger patients without hypertension.
Our findings demonstrate for the first time that hypertension is an important factor for the pathological alteration of the properties of BKC a channels in human mesenteric artery smooth muscle cells, and aging itself may also be a factor in these changes in the cells.
大电导钙激活钾通道（BKCa通道）在维持血管张力中发挥重要作用，其调节异常与血管舒张和收缩异常有关。我们检测了不同年龄患者BKCa通道特性的变化，以评估高血压和衰老对BKCa通道功能变化的影响。
采用膜片钳技术检测来自无高血压的年轻患者（年龄≤45岁）、无高血压的老年患者（年龄≥65岁）以及老年高血压患者新鲜分离的人肠系膜动脉平滑肌细胞中BKCa通道的活性。分别通过逆转录聚合酶链反应和蛋白质免疫印迹分析评估BKCa通道的mRNA和蛋白表达。结果显示，老年高血压患者动脉平滑肌细胞的全细胞电流密度、自发性瞬时外向电流和Ca(2+)敏感性显著降低；在无高血压的老年患者中，这些降低不明显，尽管在这些患者中检测到自发性瞬时外向电流有明显的降低趋势。与无高血压的年轻患者相比，老年高血压患者中BKCa亚基α和β1的mRNA和蛋白表达均显著降低，但无高血压的老年患者中未出现这种情况。
我们的研究结果首次表明，高血压是导致人肠系膜动脉平滑肌细胞中BKCa通道特性发生病理改变的重要因素，衰老本身也可能是这些细胞变化的一个因素。
