Characterization and functional role of rapid- and slow-activating delayed rectifier K + currents in atrioventricular node cells of guinea pigs.
Characterization and functional role of rapid- and slow-activating delayed rectifier K + currents in atrioventricular node cells of guinea pigs.
复制标题
豚鼠房室结细胞中快速和慢速激活延迟整流 K 电流的特征和功能作用。
DOI：
10.1007/s00424-021-02617-z
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
H. Matsuura.
中科院分区：
文献类型：
--
作者：
Yuasa;A. Kojima;X Mi;W.G;Ding;M. Omatsu-Kanbe;H. Kitagawa;H. Matsuura.
房室结是电脉冲从心房到心室的唯一传导通路，具有自发性自律性。本研究探讨了快激活和慢激活延迟整流钾电流（IKrandIKs）在房室结自律性调节中的作用。用电流钳和电压钳分别记录豚鼠房室结细胞的动作电位和IK和IK电流。免疫细胞化学证实IKrorIKs在房室结细胞中有表达，两个通道的阳性信号主要定位于细胞膜上。基础自发性自律性分别被IKrandIKs的选择性阻断剂E4031和HMR-1556同等地降低。非选择性β肾上腺素受体激动剂异丙肾上腺素显著增加动作电位的放电频率。在异丙肾上腺素存在下，IKs抑制剂HMR-1556比IKr抑制剂E4031更有效地降低动作电位的放电频率。E4031和HMR-1556在基础和β肾上腺素受体刺激条件下均延长动作电位时程并使最大舒张电位去极化。β肾上腺素受体刺激对IKr无显着影响，但异丙肾上腺素（EC 50：15 nM）浓度依赖性地增强IKs，通道激活出现显着负电压漂移。这些结果表明，在基础条件下，IKs和IKs通道对房室结动作电位复极过程的调节作用相似，但当β-肾上腺素受体被激活时，IKs的调节作用可能更为重要。
The atrioventricular (AV) node is the only conduction pathway where electrical impulse can pass from atria to ventricles and exhibits spontaneous automaticity. This study examined the function of the rapid- and slow-activating delayed rectifier K+currents (IKrandIKs) in the regulation of AV node automaticity. Isolated AV node cells from guinea pigs were current- and voltage-clamped to record the action potentials and theIKrandIKscurrent. The expression ofIKrorIKswas confirmed in the AV node cells by immunocytochemistry, and the positive signals of both channels were localized mainly on the cell membrane. The basal spontaneous automaticity was equally reduced by E4031 and HMR-1556, selective blockers ofIKrandIKs, respectively. The nonselective β-adrenoceptor agonist isoproterenol markedly increased the firing rate of action potentials. In the presence of isoproterenol, the firing rate of action potentials was more effectively reduced by theIKsinhibitor HMR-1556 than by theIKrinhibitor E4031. Both E4031 and HMR-1556 prolonged the action potential duration and depolarized the maximum diastolic potential under basal and β-adrenoceptor–stimulated conditions.IKrwas not significantly influenced by β-adrenoceptor stimulation, butIKswas concentration-dependently enhanced by isoproterenol (EC50: 15 nM), with a significant negative voltage shift in the channel activation. These findings suggest that both theIKrandIKschannels might exert similar effects on regulating the repolarization process of AV node action potentials under basal conditions; however, when the β-adrenoceptor is activated,IKsmodulation may become more important.