Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, United States.
Curr Top Membr. 2020;85:19-58. doi: 10.1016/bs.ctm.2020.01.002. Epub 2020 Feb 25.
Myogenic tone is a hall-mark feature of arterioles in the microcirculation. This pressure-induced, contractile activation of vascular smooth muscle cells (VSMCs) in the wall of these microvessels importantly contributes to the regulation and maintenance of blood pressure; blood flow to and within organs and tissues; and capillary pressure and fluid balance. Ion channels play a central role in the genesis and maintenance of myogenic tone. Mechanosensitive ion channels such as TRPC6 may serve as one of the sensors of pressure-induced membrane stress/strain, and TRPC6 along with TRPM4 channels are responsible pressure-induced VSMC depolarization that may be bolstered by the activity of Ca-activated Cl channels and inhibition of voltage-gated K (K) channels, inwardly-rectifying K (K) channels and ATP-sensitive K (K) channels. Membrane potential depolarization activates voltage-gated Ca channels (VGCCs), with CaV1.2 channels playing a central role. Calcium entry through CaV1.2 channels, which is amplified by Ca release through IP receptors in the form of Ca waves in some arterioles, provides the major source of activator calcium responsible for arteriolar myogenic tone. Stabilizing negative-feedback comes from depolarization- and Ca-induced activation of large-conductance Ca-activated K channels and depolarization-induced activation of K channels. Myogenic tone also is dampened by tonic activity of K and K channels. While much has been learned about ion channel expression and function in myogenic tone, additional studies are required to fill in our knowledge gaps due to significant regional differences in ion channel expression and function and a lack of data specifically from VSMCs in arterioles.
肌源性张力是微循环中小动脉的一个显著特征。这种压力诱导的血管平滑肌细胞（VSMCs）在这些微血管壁中的收缩激活，对血压的调节和维持、器官和组织内的血液流动以及毛细血管压力和液体平衡都有重要贡献。离子通道在肌源性张力的产生和维持中起着核心作用。机械敏感离子通道，如 TRPC6，可能作为压力诱导的膜应力/应变的传感器之一，TRPC6 与 TRPM4 通道一起负责压力诱导的 VSMC 去极化，这种去极化可能会受到 Ca 激活的 Cl 通道和电压门控 K（K）通道、内向整流 K（K）通道和 ATP 敏感 K（K）通道的活性的增强。膜电位去极化激活电压门控 Ca 通道（VGCCs），其中 CaV1.2 通道起着核心作用。CaV1.2 通道的 Ca 内流通过 IP 受体在一些小动脉中以 Ca 波的形式放大，为小动脉肌源性张力提供了主要的激活钙源。负反馈的稳定来自于大电导 Ca 激活的 K 通道的去极化和 Ca 诱导的激活以及 K 通道的去极化诱导的激活。肌源性张力也受到 K 和 K 通道的紧张活动的抑制。尽管我们已经了解了离子通道在肌源性张力中的表达和功能，但由于离子通道表达和功能的显著区域差异以及缺乏专门来自小动脉 VSMCs 的数据，还需要进一步的研究来填补我们的知识空白。
