The study of the mechanism and characteristics of triggered-activity

触发活动机制及特征研究

• 批准号: 60480229
• 负责人: HIRAOKA Masayasu
• 金额: $ 2.88万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-60480229/
• 关键词: Triggered-activity; Delayed afterdepolarization; Transient inward current; Barium ion; Aconitine; 不整脈の発生機序

Triggered-activity is one of important cellular factors for the genesis of arrhythmias. The membrane potential changes to produce triggered-activity are brought by several different mechanisms depending on the experimental conditions. To clarify the nature and the ionic mechanism of these potential changes, the microelectrode technique and voltage clamp method of the single sucrose gap or whole-cell clamp were applied to heart cells from dog, guinea pig, rabbit and frog. In the <Ca^(2+)> -overloaded conditions by exposing to the low <K^+> , high <Ca^(2+)> solutions, triggered-activity was caused by delayed afterdepolarization which was formed by the transient inward current. The characteristics of these delayed afterdepolarizations and the transient inward current were fully analyzed in terms of the responses to the electrical stimulation, as well as their voltage and time dependent natures. These informations may be used as diagnostic clues for the clinical arrhythmias based on these … More activities but different from reentry or automaticity. The study also disclosed that the transient inward current was activated not only upon repolarization but also during the depolarizing voltages, reflecting cyclic release of <Ca^(2+)> from the sarcoplasmic reticulum. The contribution of <Ca^(2+)> influx via the slow channel to the activation of the transient inward current was demonstrated by use of the <Ca^(2+)> blockers and their actions on triggered-arrhythmias can be explained by the inhibition of the <Ca^(2+)> current. The increase in the internal longitudinal resistance during the development of the delayed afterdepolarizations and triggered-activity was demonstrated by the cable analysis. The study demonstrated that the barium-induced delayed afterdepolarization and automaticity were not brought by the activation of the transient inward current, but by the <Ba^(2+)> action on the inward rectifier <K^+> current ( <I_(kl)> ). <Ba^(2+)> produced time- and voltage-dependent blockade of <I_(kl)> , which induced the delayed afterdepolarizations and automaticity. Aconitine is another agent to produce delayed afterdepolarizations and triggered-activity. In this case, the transient inward current which was triggered by the <Na^+> loading by aconitine, was shown to be a contributing factor. Therefore, triggered-activity is brought not by a single ionic mechanism, but by several different mechanisms, which may explain complex natures of these arrhythmias. Less

触发活动是心律失常发生的重要细胞因素之一。根据实验条件，膜电位变化产生触发活性是由几种不同的机制引起的。为了阐明这些电位变化的性质和离子机制，将微电极技术和单蔗糖间隙或全细胞钳的电压钳方法应用于狗、豚鼠、兔子和青蛙的心脏细胞。在暴露于低<K^+>、高<Ca^(2+)>溶液的<Ca^(2+)>过载条件下，触发活动是由瞬态内向电流形成的延迟后去极化引起的。这些延迟后去极化和瞬态内向电流的特征根据对电刺激的响应以及它们的电压和时间依赖性性质进行了充分分析。这些信息可以用作基于这些活动但不同于折返性或自动性的临床心律失常的诊断线索。研究还揭示，瞬态内向电流不仅在复极化时被激活，而且在去极化电压期间也被激活，反映了肌浆网<Ca^(2+)>的循环释放。通过使用<Ca^(2+)>阻滞剂证明了<Ca^(2+)>通过慢通道流入对瞬时内向电流激活的贡献，并且它们对触发性心律失常的作用可以通过对<Ca^(2+)>电流的抑制来解释。电缆分析证明了延迟后去极化和触发活动发展过程中内部纵向电阻的增加。研究表明，钡诱导的延迟后除极和自动性并不是由瞬态内向电流的激活带来的，而是由<Ba^(2+)>对内向整流器<K^+>电流(<I_(kl)>)的作用带来的。 <Ba^(2+)> 产生时间和电压依赖性的 <I_(kl)> 阻断，从而诱导延迟后除极和自动性。乌头碱是另一种产生延迟后去极化和触发活动的药物。在这种情况下，由乌头碱负载 <Na^+> 触发的瞬态内向电流被证明是一个影响因素。因此，触发活动不是由单一离子机制引起的，而是由几种不同的机制引起的，这可以解释这些心律失常的复杂性质。较少的

项目成果

川野誠子,平岡昌和: 薬理と治療. 13. 137-141 (1985)

Seiko Kawano，Masakazu Hiraoka：药理学和治疗。13. 137-141 (1985)。

沢登徹,平野裕司,平岡昌和: 心電図. 5. 757-767 (1985)

Toru Sawato、Yuji Hirano、Masakazu Hiraoka：心电图 5. 757-767 (1985)。

Masayasu Hiraoka: "Characteristics of triggered-activity and delayed afterdepolarization in response to the electrical stimulation." Japanese Circulation Journal. 51. (1987)

Masayasu Hiraoka：“响应电刺激的触发活动和延迟后除极的特征。”

Masayasu Hiraoka: "The inward current system activated by the <Ca^(2+)> -release from the sarcoplasmic reticulum (in Japanese)" Japanese Journal of Electrocardiology. 6. 35-40 (1986)

Masayasu Hiraoka：“由肌浆网释放<Ca^(2)>激活的内向电流系统（日语）”日本心电学杂志。

Seiko Kawano and Masayasu Hiraoka: "Rate-dependent effects of <Ca^(2+)> -antagonists on the transient inward current (in Japanese)" Pharmacology and Therapeautics. 5. 757-767 (1985)

Seiko Kawano 和 Masayasu Hiraoka：“<Ca^(2)> 拮抗剂对瞬时内向电流的速率依赖性影响（日语）”药理学和治疗学。