TRIC-A Channels in Vascular Smooth Muscle Contribute to Blood Pressure Maintenance
TRIC-A Channels in Vascular Smooth Muscle Contribute to Blood Pressure Maintenance
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DOI：
10.1016/j.cmet.2011.05.011
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发表时间：
2011-08-03
期刊：
影响因子：
29
通讯作者：
Takeshima, Hiroshi
中科院分区：
文献类型：
--
作者：
Yamazaki, Daiju;Tabara, Yasuharu;Takeshima, Hiroshi
TRIC通道亚型，即TRIC-A和TRIC-B，是细胞内单价阳离子通道，被认为介导反离子运动，促进生理性Ca（2+）从内部储存释放。由于阻力动脉中的肌源性张力增强，Tri-a-敲除小鼠在白天患上了高血压。在血管平滑肌细胞（VSMC）中有两种Ca（2+）释放机制;兰尼碱受体（RyRs）的偶然开放产生局部Ca（2+）火花以诱导超极化，而激动剂诱导的三磷酸肌醇受体（IP（3）Rs）激活引起全局Ca（2+）瞬变，引起收缩。Tric-a基因阻断可抑制RyR介导的超极化信号，刺激电压依赖性Ca（2+）内流，并通过使VSMCs内Ca（2+）库超载而增强IP（3）R介导的Ca（2+）瞬变。此外，关联分析确定了人类TRIC-A基因周围的单核苷酸多态性（SNPs），这些多态性增加了高血压风险并限制了抗高血压药物的有效性。因此，TRIC-A通道有助于维持血压，而TRIC-A SNPs可为原发性高血压的体质诊断和个体化药物治疗提供生物标志物。
TRIC channel subtypes, namely TRIC-A and TRIC-B, are intracellular monovalent cation channels postulated to mediate counter-ion movements facilitating physiological Ca(2+) release from internal stores. Tric-a-knockout mice developed hypertension during the daytime due to enhanced myogenic tone in resistance arteries. There are two Ca(2+) release mechanisms in vascular smooth muscle cells (VSMCs); incidental opening of ryanodine receptors (RyRs) generates local Ca(2+) sparks to induce hyperpolarization, while agonist-induced activation of inositol trisphosphate receptors (IP(3)Rs) evokes global Ca(2+) transients causing contraction. Tric-a gene ablation inhibited RyR-mediated hyperpolarization signaling to stimulate voltage-dependent Ca(2+) influx, and adversely enhanced IP(3)R-mediated Ca(2+) transients by overloading Ca(2+) stores in VSMCs. Moreover, association analysis identified single-nucleotide polymorphisms (SNPs) around the human TRIC-A gene that increase hypertension risk and restrict the efficiency of antihypertensive drugs. Therefore, TRIC-A channels contribute to maintaining blood pressure, while TRIC-A SNPs could provide biomarkers for constitutional diagnosis and personalized medical treatment of essential hypertension.