Hypoxic Conditions Promote Rhythmic Contractile Oscillations Mediated by Voltage-Gated Sodium Channels Activation in Human Arteries.

ABSTRACT: 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_v), 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_v 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_Na current. Various Na_v genes, encoding α-subunit isoforms sensitive (Na_v 1.2; 1.3; 1.7) and resistant (Na_v 1.5) to TTX, were detected both in arterial tissue and in SMCs. Na_v 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_v 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⁺/Ca²⁺ exchanger, Na⁺/K⁺-ATPase and the cardiac Na_v channel. These results highlight the role of Na_v as a novel key element in the vasomotion of human arteries. Hypoxia promotes activation of Na_v channels involved in the initiation of rhythmic oscillatory contractile activity.

SUBMITTER: Virsolvy A 

PROVIDER: S-EPMC7961413 | biostudies-literature |

REPOSITORIES: biostudies-literature