Submitted on September 3, 2008
Revised on October 2, 2008
Accepted on October 29, 2008
Function and Role of Voltage-Gated Sodium Channel (NaV1.7) Expressed in Aortic Smooth Muscle Cells
Kentaro Meguro1*, Haruko Iida1, Haruhito Takano1, Toshihiro Morita, Masataka Sata, Ryozo Nagai2, and Toshiaki Nakajima3
1 University of Tokyo Graduate School of Medicine
2 Univ. of Toky
3 University of Tokyo
* To whom correspondence should be addressed. E-mail: meguro{at}med.email.ne.jp.
Background: Voltage-gated sodium 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. Methods and Results: In whole-cell voltage clamp, INa was observed at potential positive to -40 mV, was blocked by 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 treatment with SCN9A siRNA (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 secretion of matrix metalloproteinase-2 6 and 12 h after the treatment (p<0.01, 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, while 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. Conclusions: 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 the balloon injury, suggesting a potential role for NaV1.7 in the progression of intimal hyperplasia.
