Inserm, Umr-S 1180, Université Paris-Saclay, Châtenay-Malabry, France.
Inserm, Umr-S 1180, Université Paris-Saclay, Châtenay-Malabry, France.
Pharmacol Ther. 2020 May;209:107499. doi: 10.1016/j.pharmthera.2020.107499. Epub 2020 Feb 15.
Numerous mediators and drugs regulate blood flow or arterial pressure by acting on vascular tone, involving cyclic nucleotide intracellular pathways. These signals lead to regulation of several cellular effectors, including ion channels that tune cell membrane potential, Ca influx and vascular tone. The characterization of these vasocontrictive or vasodilating mechanisms has grown in complexity due to i) the variety of ion channels that are expressed in both vascular endothelial and smooth muscle cells, ii) the heterogeneity of responses among the various vascular beds, and iii) the number of molecular mechanisms involved in cyclic nucleotide signalling in health and disease. This review synthesizes key data from literature that highlight ion channels as physiologically relevant effectors of cyclic nucleotide pathways in the vasculature, including the characterization of the molecular mechanisms involved. In smooth muscle cells, cation influx or chloride efflux through ion channels are associated with vasoconstriction, whereas K efflux repolarizes the cell membrane potential and mediates vasodilatation. Both categories of ion currents are under the influence of cAMP and cGMP pathways. Evidence that some ion channels are influenced by CN signalling in endothelial cells will also be presented. Emphasis will also be put on recent data touching a variety of determinants such as phosphodiesterases, EPAC and kinase anchoring, that complicate or even challenge former paradigms.
许多介质和药物通过作用于血管张力来调节血流或动脉血压，涉及环核苷酸细胞内途径。这些信号导致几种细胞效应器的调节，包括调节细胞膜电位、Ca2+内流和血管张力的离子通道。由于以下几个原因，这些缩血管或扩血管机制的特征变得越来越复杂：i）在血管内皮细胞和平滑肌细胞中表达的离子通道种类繁多，ii）各种血管床之间的反应异质性，iii）在健康和疾病中涉及环核苷酸信号的分子机制的数量。 这篇综述综合了文献中的关键数据，强调了离子通道作为血管中环核苷酸途径的生理相关效应器，包括对涉及的分子机制的描述。在平滑肌细胞中，阳离子内流或氯离子通过离子通道外流与血管收缩有关，而 K+外流使细胞膜电位复极化并介导血管舒张。这两类离子电流都受 cAMP 和 cGMP 途径的影响。还将介绍一些证据表明，内皮细胞中的一些离子通道受 CN 信号的影响。还将重点介绍最近的数据，涉及各种决定因素，如磷酸二酯酶、EPAC 和激酶锚定，这些因素使以前的范例变得复杂甚至受到挑战。
