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

点击翻译按钮获取中文摘要

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.