Voltage-gated sodium channels are involved in vasomotion of human arteries

Abstract

Voltage-gated sodium channels (Na v ) are responsible for the initiation and propagation of action potential in excitable cells. In vascular smooth muscle cells (VSMCs), usually electrically quiescent, their presence and functional impact are less well-defined, especially in human arteries. In the present study, we determined Na v channels gene expression profile and assessed the effect of Na v channel activator veratridine on human arteries. Human uterine arteries obtained from women undergoing hysterectomy were used. I Na currents were electrophysiologically recorded on isolated VSMCs. Isometric tensions were recorded ex vivo on uterine artery rings in response to Na v channel agonist (veratridine) and antagonist (tetrodotoxin, TTX) under physiological and hypoxic conditions. A TTX-sensitive and fast inactivating I Na current was recorded in VSCMs isolated from human uterine artery. Various Na v channel genes were detected, corresponding to TTX-sensitive (Na v 1.2; 1.3; 1.7) and TTX-resistant (Na v 1.5) alpha-subunit isoforms. Under hypoxic conditions, promotion of Na v channel activity by veratridine triggered rhythmic oscillations in vascular tone of uterine arterial rings similar to vasomotion. This rhythmic activity was abolished by TTX (1 to 0.01 μM) and attenuated by the calcium antagonist nifedipine (1 μM). Na v channel are present in VSMCs of human arteries where they are functionally coupled to contractile activity. Under hypoxic condition, they could initiate, ex vivo, rhythmic contractile activity reminiscent of vasomotion. This is the first demonstration of Na v channels contribution to this complex phenomenon.