Different Effects of Hypertension and Age on the Function of Large Conductance Calcium- and Voltage-Activated Potassium Channels in Human Mesentery Artery Smooth Muscle Cells.
Different Effects of Hypertension and Age on the Function of Large Conductance Calcium- and Voltage-Activated Potassium Channels in Human Mesentery Artery Smooth Muscle Cells.
复制标题
高血压和年龄对人类肠系膜平滑肌细胞中钙和电压激活的钾通道功能的功能不同。
DOI：
10.1161/jaha.116.003913
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发表时间：
2016-09-14
影响因子：
5.4
通讯作者：
Yang Y
中科院分区：
文献类型：
--
作者：
Cheng J;Mao L;Wen J;Li PY;Wang N;Tan XQ;Zhang XD;Zeng XR;Xu L;Xia XM;Xia D;He K;Su S;Yao H;Yang Y
大电导钙和电压激活钾通道（BKC a通道）在维持血管张力中起重要作用，其失调与异常的血管舒张和收缩相关。我们检测了不同年龄患者BKC α通道特性的变化，以评估高血压和衰老对BKC α通道功能变化的影响。应用膜片钳技术检测年龄≤45岁、≥65岁和老年高血压患者肠系膜动脉平滑肌细胞BKC α通道的活性。用逆转录聚合酶链反应（RT-PCR）和蛋白质印迹法（Western blot）检测BKC α通道mRNA和蛋白质的表达。结果显示，在老年高血压患者中，动脉平滑肌细胞的全细胞电流密度、自发瞬时外向电流和Ca 2+敏感性显著降低;在无高血压的老年患者中，这些降低不显著，尽管在这些患者中检测到明显的自发瞬时外向电流趋势。老年高血压患者BKC α亚基α和β1的mRNA和蛋白表达均显著低于青年非高血压患者，而老年非高血压患者BKC α亚基α和β1的mRNA和蛋白表达无显著性差异。我们的研究结果首次表明，高血压是人类肠系膜动脉平滑肌细胞中BKC α通道特性病理改变的重要因素，衰老本身也可能是细胞中这些变化的一个因素。
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 Ca2+ 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.