Functional role of voltage‐gated Na+ channels in rat mesenteric arteries

Abstract

We have previously reported that voltage-gated Na+ channels (NaV) are expressed in freshly dissociated smooth muscle cells from the mouse portal vein, which displays spontaneous, rhythmic contractions. However, the physiological function of NaV in smooth muscle is controversial. Here, we explored the role of NaV in arterial vascular contractility. Isolated mesenteric arteries from male Wistar rats (200–300g) were mounted in a wire-myograph for tension recording. The NaV activator veratridine elicited concentration-dependent (1–30μM), but endothelium-independent, contractions. These contractions (at 10μM, 8.8±0.7mN; n=8) were greatly inhibited by 1μM tetrodotoxin (TTX), a NaV blocker (1.3±0.9mN, n=4) and abolished in Na+-free physiological salt solution (−0.2±0.1mN, n=4). To probe the expression of NaV isoforms (NaV1.1–1.9), we used conventional reverse transcriptase polymerase chain reaction (RT-PCR) with mRNA extracted from the isolated vessels. The presence of TTX-sensitive NaV isoforms (1.2, 1.3, 1.6 and 1.7) was evident. Based on these data, we propose that functional NaV are expressed in arteries without spontaneous rhythmic contractions and may play a role in the regulation of vascular tone. We acknowledge the financial support from St George's University of London and British Heart Foundation