Results: We identified three Nav transcripts in the whole rat aorta: Nav1.2, Nav1.3, and. Nav1.5. The Nav1.2 isoform was found both in the intact media and in ...
1.5 VOLTAGE-GATED Na CHANNELS REGULATE CONTRACTION OF RAT AORTA Fort A1, Cordaillat M1, Thollon C3, Salazar G1, Mechaly I2, Villeneuve N3, Vilaine JP3, Richard S1, Virsolvy A1 1
Inserm U637, Montpellier, France, 2Inserm U583, Montpellier, France, 3Institut de Recherches Servier, Neuilly-sur Seine, France Background: There is increasing evidence for the presence of voltage-gated sodium channels (Nav) in arterial myocytes. However, there is no information of whether or not Nav play a functional role in arteries. Methods: Identification of Nav transcripts and protein localization in rat aortas were performed by use of real-time RT-PCR and immunohistochemistry. Vascular reactivity was investigated on isometric tension of endothelium denuded aortic rings. Results: We identified three Nav transcripts in the whole rat aorta: Nav1.2, Nav1.3, and Nav1.5. The Nav1.2 isoform was found both in the intact media and in myocytes freshly isolated from the media. Nav channels were localized in the myocytes all throughout the media. Using veratridine and TTX, we unmasked a functional role of Na v channels in the control of contraction. We discriminated two different mechanisms of regulation highly sensitive to TTX (nanomolar range). The first one, activated by veratridine at resting tension (EC50 = 34.2±4.8 µM), was abolished by the α1-adrenergic receptors antagonist prazosin (10 µM). This could be accounted for by an effect of veratridine on Nav channels localized at perivascular sympathetic nerves terminals, promoting noradrenaline release and, thereby, contraction. The other component, resistant to prazosin, was unmasked with low KCl (2-10 mmol/L) inducing moderate membrane depolarizations. This is consistent with a contribution of Nav channels located at the arterial myocytes level. Conclusion: We establish a novel paradigm for a role for Nav channels in vascular physiology, and suggest that the brain-type TTX-sensitive Nav1.2 isoform contributes to contraction of aortic myocytes.
