Ectopic activities in pulmonary veins initiating atrial fibrillation

起源于肺静脉心肌袖的自发电活动在房颤的发生和维持中起重要作用，但对肺静脉致心律失常的离子机制知之甚少。我们研究了离子通道在兔和大鼠肺静脉中的表达，并对其在窦房结和心房肌中的表达进行了比较。超极化激活通道(HCN1、HCN4)和Cav1.3型L钙通道mRNAs在窦房结中大量表达，但在肺静脉中的表达低于在心房肌中的表达。肺静脉的内向整流钾通道(Kir2.1、Kir2.2)、心型钠通道(NaV1.5)和钙调节蛋白(Ryanodine受体和SERCA)的mRNA量均低于心房肌。这些结果表明，肺静脉独特的离子通道表达谱可能是导致心律失常的基础，如传导障碍和细胞内钙超载。心房颤动通常与心房扩张有关。我们研究了牵张激活通道(SAC)阻滞剂对心房内压力超负荷的兔心心房颤动易感性的影响。GA^&lt；3+&gt；减少了拉伸引起的脆弱性。合成肽(据报道可阻断SAC的一部分)和氯离子通道阻滞剂对压力超负荷时的心房颤动倾向没有显著影响。阻断SAC可能是治疗心房压力升高条件下房颤的一种新的抗心律失常方法。

Spontaneous electrical activities originating from the pulmonary vein myocardial sleeves play important roles in the initiation and maintenance of atrial fibrillation, but little is known about the ionic mechanisms of arrhytmogenic activities in the pulmonary veins. We investigated ion channel expression in rabbit and rat pulmonary veins and compared those in the sinoatiral node and atrial muscle. Hyperpolarization-activated channels (HCN1, HCN4) and Cav1.3 L-type Ca channel mRNAs were abundantly expressed in the sinoatrial node but their expression in the pulmonary veins was less than in the atrial muscle. Inward rectifier K channels (Kir2.1, Kir2.2), cardiac type Na channel (Nav1.5) and Ca-handling proteins (ryanodine receptor and SERCA) mRNAs were lower in the pulmonary veins than in atrial muscle. These results suggest that the unique ion channel expression profile in the pulmonary veins may underlie arrhythmogenic substrates such as impaired conduction and intracellular Ca overload.Atrial fibrillation is often associated with atrial dilatation. We investigated the effects of stretch-activated channel (SAC) blockers on the vulnerability of atrial fibrillation in intra-atrial pressure-overloaded rabbit hearts. Ga^<3+> reduced the stretch-induced vulnerability. Synthesized peptides, which are reported to block a subset of SAC, and Cl^-channel blockers have no significant effects on atrial fibrillation propensity during pressure overload. Blockade of SAC might be a novel antiarrhythmic approach to atrial fibrillation under conditions of increased atrial pressure.