Function and role of voltage-gated sodium channel Na(V)1.7 expressed in aortic smooth muscle cells

Meguro K, Iida H, Takano H, Morita T, Sata M, Nagai R, Nakajima T. Function and role of voltage-gated sodium channel Na(V)1.7 expressed in aortic smooth muscle cells. Am J Physiol Heart Circ Physiol 296: H211-H219, 2009. First published October 31, 2008; doi: 10.1152/ajpheart.00960.2008. - Voltage-gated Na+ channel currents (I-Na) are expressed in several types of smooth muscle cells. The purpose of this study was to evaluate the expression of I-Na, its functional role, pathophysiology in cultured human (hASMCs) and rabbit aortic smooth muscle cells (rASMCs), and its association with vascular intimal hyperplasia. In whole cell voltage clamp, INa was observed at potential positive to -40 mV, was blocked by tetrodotoxin (TTX), and replacing extracellular Na+ with N-methyl-D-glucamine in cultured hASMCs. In contrast to native aorta, cultured hASMCs strongly expressed SCN9A encoding Na(V)1.7, as determined by quantitative RT-PCR. I-Na was abolished by the treatment with SCN9A small-interfering (si) RNA (P < 0.01). TTX and SCN9A siRNA significantly inhibited cell migration (P < 0.01, respectively) and horseradish peroxidase uptake (P < 0.01, respectively). TTX also significantly reduced the secretion of matrix metalloproteinase-2 6 and 12 h after the treatment (P < 0.01 and P < 0.05, respectively). However, neither TTX nor siRNA had any effect on cell proliferation. L-type Ca2+ channel current was recorded, and I-Na was not observed in freshly isolated rASMCs, whereas TTX-sensitive I-Na was recorded in cultured rASMCs. Quantitative RT-PCR and immunostaining for Na(V)1.7 revealed the prominent expression of SCN9A in cultured rASMCs and aorta 48 h after balloon injury but not in native aorta. In conclusion, these studies show that I-Na is expressed in cultured and diseased conditions but not in normal aorta. The Na(V)1.7 plays an important role in cell migration, endocytosis, and secretion. Na(V)1.7 is also expressed in aorta after balloon injury, suggesting a potential role for Na(V)1.7 in the progression of intimal hyperplasia.