PhyMedExp, Université de Montpellier, INSERM, CNRS, 34495 Montpellier, France.
CHU de Montpellier, 34495 Montpellier, France.
Int J Mol Sci. 2021 Mar 4;22(5):2570. doi: 10.3390/ijms22052570.
Arterial smooth muscle exhibits rhythmic oscillatory contractions called vasomotion and believed to be a protective mechanism against tissue hypoperfusion or hypoxia. Oscillations of vascular tone depend on voltage and follow oscillations of the membrane potential. Voltage-gated sodium channels (Na), responsible for the initiation and propagation of action potentials in excitable cells, have also been evidenced both in animal and human vascular smooth muscle cells (SMCs). For example, they contribute to arterial contraction in rats, but their physiopathological relevance has not been established in human vessels. In the present study, we investigated the functional role of Na in the human artery. Experiments were performed on human uterine arteries obtained after hysterectomy and on SMCs dissociated from these arteries. In SMCs, we recorded a tetrodotoxin (TTX)-sensitive and fast inactivating voltage-dependent I current. Various Na genes, encoding α-subunit isoforms sensitive (Na 1.2; 1.3; 1.7) and resistant (Na 1.5) to TTX, were detected both in arterial tissue and in SMCs. Na channels immunostaining showed uniform distribution in SMCs and endothelial cells. On arterial tissue, we recorded variations of isometric tension, ex vivo, in response to various agonists and antagonists. In arterial rings placed under hypoxic conditions, the depolarizing agent KCl and veratridine, a specific Na channels agonist, both induced a sustained contraction overlaid with rhythmic oscillations of tension. After suppression of sympathetic control either by blocking the release of catecholamine or by antagonizing the target adrenergic response, rhythmic activity persisted while the sustained contraction was abolished. This rhythmic activity of the arteries was suppressed by TTX but, in contrast, only attenuated by antagonists of calcium channels, Na/Ca exchanger, Na/K-ATPase and the cardiac Na channel. These results highlight the role of Na as a novel key element in the vasomotion of human arteries. Hypoxia promotes activation of Na channels involved in the initiation of rhythmic oscillatory contractile activity.
动脉平滑肌表现出称为血管舒缩的有节奏的振荡收缩，被认为是防止组织低灌注或缺氧的保护机制。血管张力的振荡依赖于电压，并跟随膜电位的振荡。电压门控钠通道（Na）负责在可兴奋细胞中产生和传播动作电位，在动物和人类血管平滑肌细胞（SMC）中也有证据表明。例如，它们有助于大鼠的动脉收缩，但它们在人类血管中的生理病理学相关性尚未确定。在本研究中，我们研究了 Na 在人类动脉中的功能作用。实验在子宫切除术切除后的人子宫动脉和从这些动脉分离的 SMC 上进行。在 SMC 中，我们记录了河豚毒素（TTX）敏感且快速失活的电压依赖性 I 电流。在动脉组织和 SMC 中均检测到编码对 TTX 敏感（Na 1.2；1.3；1.7）和抗性（Na 1.5）的α亚基同工型的各种 Na 基因。Na 通道免疫染色显示在 SMC 和内皮细胞中均匀分布。在动脉组织上，我们记录了对各种激动剂和拮抗剂的等长张力变化，在体外。在置于缺氧条件下的动脉环中，去极化剂 KCl 和辣椒素，一种特定的 Na 通道激动剂，均诱导持续收缩，并伴有张力的有节奏振荡。在抑制交感神经控制后，无论是通过阻断儿茶酚胺的释放还是通过拮抗靶向肾上腺素能反应，节律性活动持续存在，而持续收缩被消除。这种动脉的节律性活动被 TTX 抑制，但相反，仅被钙通道拮抗剂、Na/Ca 交换体、Na/K-ATP 酶和心脏 Na 通道拮抗剂减弱。这些结果强调了 Na 作为人类动脉血管舒缩的新型关键因素的作用。缺氧促进参与节律性收缩活动启动的 Na 通道的激活。
