Investigation on possible link between Ist and CaV1.3 RNA editing

窦房结(SAN)起搏细胞持续的内向Na+电流(Ist)参与了起搏器的活动，但这一电流的未知分子相关性限制了人们对其在起搏器活动中的意义的理解。本研究的目的是：1)研究L钙通道CaV1.3亚单位与Ist功能表达水平的关系；2)鉴定核糖核酸编辑介导的CaV1.3变异体。Ist密度与L型钙电流(ICa，L)的大小呈正相关。在CaV1.3、ICA基因缺失的基因敲除小鼠中，L的表达水平显著降低，并伴随着Ist的完全丧失。使用第二代测序仪对CaV1.3转录本进行的综合分析表明，在钙离子选择性过滤器中存在带有残基变化的罕见变体。这些发现提示，起搏细胞中的Ist是由CaV1.3变异体Ist介导的。

The sustained inward Na+ current (Ist) in sinoatrial node (SAN) pacemaker cells has been suggested to contribute to the pacemaker activity, although unknown molecular correlates of this current limits the understanding of its significance in the pacemaker activity. The purpose of this study was 1) to examine the relationship between L-type Ca2+ channel CaV1.3 subunit and Ist in their functional expression levels, and 2) to identify the RNA editing-mediated CaV1.3 variants. The density of Ist was positively correlated with the magnitude of L-type Ca2+ current (ICa,L). In knock-out mice with disruption of CaV1.3, ICa,L was significantly reduced, which was accompanied by a complete loss of Ist. Comprehensive analysis of CaV1.3 transcripts using the second generation sequencer revealed the presence of rare variants with residue changes in the Ca2+ selectivity filter. These findings suggest that Ist is mediated by CaV1.3 variants Ist in SAN pacemaker cells.