Hübner Christian A, Schroeder Björn C, Ehmke Heimo
Institut für Humangenetik, Universitätsklinikum Jena, Friedrich-Schiller Universität Jena, Kollegiengasse 10, 07743, Jena, Germany,
Pflugers Arch. 2015 Mar;467(3):605-14. doi: 10.1007/s00424-014-1684-y. Epub 2015 Jan 16.
Recent studies suggest that primary changes in vascular resistance can cause sustained changes in arterial blood pressure. In this review, we summarize current knowledge about Cl(-) homeostasis in vascular smooth muscle cells. Within vascular smooth muscle cells, Cl(-) is accumulated above the electrochemical equilibrium, causing Cl(-) efflux, membrane depolarization, and increased contractile force when Cl(-) channels are opened. At least two different transport mechanisms contribute to raise [Cl(-)] i in vascular smooth muscle cells, anion exchange, and cation-chloride cotransport. Recent work suggests that TMEM16A-associated Ca(2+)-activated Cl(-) currents mediate Cl(-) efflux in vascular smooth muscle cells leading to vasoconstriction. Additional proteins associated with Cl(-) flux in vascular smooth muscle are bestrophins, which modulate vasomotion, the volume-activated LRRC8, and the cystic fibrosis transmembrane conductance regulator (CFTR). Cl(-) transporters and Cl(-) channels in vascular smooth muscle cells (VSMCs) significantly contribute to the physiological regulation of vascular tone and arterial blood pressure.
近期研究表明，血管阻力的原发性改变可导致动脉血压的持续性变化。在本综述中，我们总结了目前关于血管平滑肌细胞中氯离子（Cl⁻）稳态的知识。在血管平滑肌细胞内，Cl⁻在电化学平衡之上蓄积，当Cl⁻通道开放时，会导致Cl⁻外流、膜去极化以及收缩力增加。至少有两种不同的转运机制有助于提高血管平滑肌细胞内的Cl⁻浓度，即阴离子交换和阳离子-氯离子共转运。近期研究表明，与跨膜蛋白16A（TMEM16A）相关的钙激活Cl⁻电流介导血管平滑肌细胞中的Cl⁻外流，导致血管收缩。与血管平滑肌中Cl⁻通量相关的其他蛋白包括调节血管运动的贝斯特rophin蛋白、容积激活的富含亮氨酸重复序列8（LRRC8）以及囊性纤维化跨膜传导调节因子（CFTR）。血管平滑肌细胞（VSMC）中的Cl⁻转运体和Cl⁻通道对血管张力和动脉血压的生理调节起着重要作用。
