Malécot Claire O, Bredeloux Pierre, Findlay Ian, Maupoil Véronique
CNRS ERL 7368, Laboratoire Signalisation et Transports Ioniques Membranaires, Universités de Poitiers et François-Rabelais de Tours, France; Groupe Physiologie des Cellules Cardiaques et Vasculaires, Université François-Rabelais, Tours, France.
J Cardiovasc Electrophysiol. 2015 Mar;26(3):311-9. doi: 10.1111/jce.12572. Epub 2014 Dec 2.
Ectopic activity arising from pulmonary veins (PV) plays a prominent role in the onset of atrial fibrillation in humans. Rat PV cardiac muscle cells have a lower resting membrane potential (RMP) than the left atria (LA) and presents in the presence of norepinephrine an automatic activity, which occurs in bursts. This study investigated the role of Na channels upon the RMP and the catecholaminergic automatic activity (CAA) in PV cardiac muscle.
RMP and CAA experiments were performed in male Wistar rat PV. Whole-cell INa was recorded in isolated PV and LA cardiomyocytes. PV has a higher tetrodotoxin (TTX)-sensitive basal Na(+) permeability than the LA, due to a ∼ 5 mV more negative Na window current in the former tissue. TTX, quinidine, and ranolazine (1 to 10 μM each) decreased CAA incidence and arrhythmias by increasing burst intervals because of a reduction of the slope of slow depolarization between bursts. TTX and ranolazine also reduced burst duration. At 1 Hz, 10 μM quinidine, ranolazine, and TTX inhibited peak INa by 33%, 28%, and 98%, respectively. Each reduced the Na window current. There was no evidence for a TTX- or ranolazine-sensitive late Na current.
Na channels confer a TTX-sensitive basal Na(+) permeability to rat PV cardiac muscle cells and contribute to the slope of slow depolarization between bursts of CAA. Na channel blockers act mostly via reduction of the Na window current. Ranolazine also has an anti-α1 adrenergic effect, which contributed to its antiarrhythmic effect.
肺静脉（PV）产生的异位活动在人类房颤的发生中起重要作用。大鼠PV心肌细胞的静息膜电位（RMP）低于左心房（LA），并且在去甲肾上腺素存在的情况下呈现出自动活动，这种活动呈阵发性发生。本研究调查了钠通道在PV心肌细胞的RMP和儿茶酚胺能自动活动（CAA）中的作用。
对雄性Wistar大鼠的PV进行了RMP和CAA实验。在分离的PV和LA心肌细胞中记录全细胞钠电流（INa）。由于PV组织中钠窗电流比LA组织约负5 mV，PV具有比LA更高的对河豚毒素（TTX）敏感的基础钠（+）通透性。TTX、奎尼丁和雷诺嗪（各1至10 μM）通过增加阵发性间隔降低了CAA发生率和心律失常，这是因为降低了阵发性之间缓慢去极化的斜率。TTX和雷诺嗪也缩短了阵发性持续时间。在1 Hz时，10 μM奎尼丁、雷诺嗪和TTX分别抑制峰值INa 33%、28%和98%。每种药物都降低了钠窗电流。没有证据表明存在对TTX或雷诺嗪敏感的晚钠电流。
钠通道赋予大鼠PV心肌细胞对TTX敏感的基础钠（+）通透性，并有助于CAA阵发性之间缓慢去极化的斜率。钠通道阻滞剂主要通过降低钠窗电流起作用。雷诺嗪还具有抗α1肾上腺素能效应，这有助于其抗心律失常作用。
