心房颤动（房颤）是心房电活动的紊乱，导致心房失去有效收缩，在老年人中发病率接近10%，房颤导致心脏排血量下降从而诱发或加重充血性心力衰竭，增加缺血性脑卒中的风险。延迟钠电流增加致心房触发活动和引起房颤及抑制内源性和增大的延迟钠电流在治疗房颤中是新课题。我们课题组与国外研究室合作，利用分离的心室肌细胞研究发现，心肌细胞内钙含量增多时，过多的钙离子一方面通过钠钙交换体（NCX）途径，在排出胞浆内钙离子的同时引起钠内流增多；另一方面过多的钙离子能够进一步激活钙调蛋白激酶II（27%）和蛋白激酶C （62%）通路，激活的钙调蛋白激酶II（CaMK II）和蛋白激酶C（PKC）通过磷酸化Nav1.5 钠通道蛋白使其激活，进一步增大延迟钠电流。因此我们提出下面的假设：蛋白激酶C通过对Na1.5通道的磷酸化介导心房肌细胞延迟钠电流的增大，促进心房肌细胞的触发活动及房颤的发

Atrial fibrillation (AF) is a disorder of atrial electrical activity, resulting in the loss of effective atrial contraction. The incidence is close to 10% in the elderly. Atrial fibrillation leads to decreased cardiac output, inducing or aggravating congestive heart failure, increasing the risk of ischemic stroke and total mortality. Prevention and treatment of atrial fibrillation has become one of the hottest topics in the field of heart research. Increased late sodium currents induced atrial fibrillation is a new topic in the treatment of atrial fibrillation. Our group in collaboration with foreign laboratories, with the use of isolated cardiomyocytes, found that increase in the intracellular calcium content, led to discharge of cytosolic calcium and at the same time caused an increase in the flow of sodium by the sodium calcium exchanger (NCX) pathway; on the other hand, excess calcium could further activate calmodulin kinase II (27%) and protein kinase C (62%) pathway, activated calmodulin kinase II (CaMK II) and Protein kinase C (PKC) phosphorylate Nav1.5 sodium channel protein to make it.active, further increasing the late sodium current. We propose the following hypothesis: The phosphorylation of Na1.5 mediated by protein kinase C in atrial myocytes increases late sodium current, promoting triggered activity in atrial myocytes and atrial fibrillation.

异丙肾上腺素（ISO）是一种β受体激动剂，也可以激活 CaMKII。β受体激活可以通增加心脏自主性诱发房颤。 ISO也可以通过增加细胞内钙浓度引起触发活动而导致房颤。重要的是 ISO 也可以激活 CaMK-II 引起晚钠电流增大。晚钠电流增大也会导致触发活动，导致心脏复极离散度增大，在复极不均一的心脏，期前收缩即可诱发房颤。有趣的是，钙调蛋白激酶诱发的晚钠电流增大又可以引起细胞内钠离子浓度升高，继而引起细胞内钙浓度升高。钙浓度升高又会激活钙调蛋白激酶从而导致恶性循环，诱发房颤。我们的研究结果显示异丙肾上腺素可以浓度依赖性增加房颤的诱发窗口，房颤负荷以及房颤发生率，降低心房不应期。钙调蛋白激酶抑制剂KN-93和晚钠电流抑制剂雷诺嗪Ran分别可以浓度依赖性降低异丙肾上腺素ISO（15nM）诱导的房颤诱发窗口，房颤负荷以及房颤发生率，增加心房不应期。分子生物学研究结果显示钙调蛋白激酶抑制剂KN-93和晚钠电流抑制剂雷诺嗪Ran分别可以降低异丙肾上腺素诱导的CaMKIIδ、Nav1.5蛋白表达和磷酸化水平。