Department of Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama Funabashi, Chiba 274-8510, Japan.
Int J Mol Sci. 2024 Nov 18;25(22):12367. doi: 10.3390/ijms252212367.
The pulmonary vein wall contains a myocardial layer whose ectopic automaticity is the major cause of atrial fibrillation. This review summarizes the results obtained in isolated pulmonary vein myocardium from small experimental animals, focusing on the studies with the guinea pig. The diversity in the action potential waveform reflects the difference in the repolarizing potassium channel currents involved. The diastolic depolarization, the trigger of automatic action potentials, is caused by multiple membrane currents, including the Na-Ca exchanger current and late I. The action potential waveform and automaticity are affected differentially by α- and β-adrenoceptor stimulation. Class I antiarrhythmic drugs block the propagation of ectopic electrical activity of the pulmonary vein myocardium through blockade of the peak I. Some of the class I antiarrhythmic drugs block the late I and inhibit pulmonary vein automaticity. The negative inotropic and chronotropic effects of class I antiarrhythmic drugs could be largely attributed to their blocking effect on the Ca channel rather than the Na channel. Such a comprehensive understanding of pulmonary vein automaticity and class I antiarrhythmic drugs would lead to an improvement in pharmacotherapy and the development of novel therapeutic agents for atrial fibrillation.
肺静脉壁含有心肌层，其异位自动性是房颤的主要原因。这篇综述总结了从小型实验动物分离的肺静脉心肌中获得的结果，重点介绍了豚鼠的研究。动作电位波形的多样性反映了涉及的复极钾通道电流的差异。舒张期去极化是自动动作电位的触发，由多种膜电流引起，包括 Na-Ca 交换体电流和晚期 I。α-和β-肾上腺素能受体刺激对动作电位和自动性的影响不同。I 类抗心律失常药物通过阻断峰值 I 来阻断肺静脉心肌异位电活动的传播。一些 I 类抗心律失常药物阻断晚期 I 并抑制肺静脉自动性。I 类抗心律失常药物的负性肌力和负性频率作用主要归因于它们对钙通道的阻断作用，而不是钠通道。对肺静脉自动性和 I 类抗心律失常药物的这种全面理解将导致对房颤的药理学治疗的改善和新型治疗剂的开发。
