L型钙通道CaV1.2在动脉平滑肌收缩中起着非常重要的作用，其功能紊乱与高血压密切相关。剪接体作为调控钙离子通道一个重要的转录后调控机制，已发现在神经发育中受到Fox蛋白的调控。但Fox蛋白是否参与高血压血管中L型钙离子通道的剪接体调控目前还不清楚。我们的前期研究表明高血压大鼠血管内CaV1.2剪接体exon 9*表达升高，而exon 33表达降低。更为重要的是，血管内Fox蛋白的表达也降低。所以，我们推测Fox蛋白调控血管中CaV1.2剪接体表达改变，从而改变血管平滑肌钙离子通道特征，进而调控血管舒缩和血压。在此，我们将利用过表达质粒、siRNA和转录扫描等分子生物学技术，并利用全细胞膜片钳、体外血管舒缩检测和在体血压检测等生理学实验在细胞、器官和整体水平验证Fox蛋白对CaV1.2剪接体的调控作用。这一项目将为我们提供高血压发病的一个重要机制，并有望为治疗高血压提供一个崭新的治疗靶点。

L-type CaV1.2 channels have a dominant role in arterial smooth muscle contraction and its dysregulation is therefore important in hypertension. Splicing events, as an important mechanism of post-transcript modulation in L-type calcium channels, has been found to invovle in the neural development, and which is regulated by Fox proteins. Whether Fox proteins take part in the modulation of CaV1.2 calcium channel splicing in the hypertensive arteries remains unknown. Our preliminary data indicated the expressiones of the alternative splice variants of CaV1.2 calcium channels have been changed: the expression of exon 9* increased; while exon 33 decreased. More importantly, the expression of the Fox proteins also changed in the hypertensive arteries, which was associated with the level of exon 9* and exon 33. Therefore, we presume that Fox proteins regulate the splicing of CaV1.2 calcium channels in the arteries, in turn change these channel properties, thus modulate the arterial constriction and blood pressure. Here, we will use molecular biological techniques, whole-cell patch clamp, in-vitro arterial constriction assay and in-vivo blood pressure monitor to investigate the modulation of CaV1.2 calcium channel splicing by Fox proteins from cellualr, organ and even whole animal levels. This project can illustrate an important mechanism, which never known before, in the development of hypertension, and may provide a newly promissing theraputic target in the management of vascular hypertension.