Voltage-gated Na+ channel currents ( INa) are expressed in several types of smooth muscle cells. The purpose of this study was to evaluate the expression of INa, 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 NaV1.7, as determined by quantitative RT-PCR. INa 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 INa was not observed in freshly isolated rASMCs, whereas TTX-sensitive INa was recorded in cultured rASMCs. Quantitative RT-PCR and immunostaining for NaV1.7 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 INa is expressed in cultured and diseased conditions but not in normal aorta. The NaV1.7 plays an important role in cell migration, endocytosis, and secretion. NaV1.7 is also expressed in aorta after balloon injury, suggesting a potential role for NaV1.7 in the progression of intimal hyperplasia.
Effect of gene delivery of NOS isoforms on intimal hyperplasia and endothelial regeneration after balloon injury
