Delayed Afterdepolarization and Triggered Activity, and the Effects of Antiarrhythmic Agents on these Abnormalities in the Atrioventricular Node and Ventricle

延迟后除极和触发活动，以及抗心律失常药物对房室结和心室异常的影响

• 批准号: 62570406
• 负责人: WATANABE Yoshio
• 金额: $ 1.28万
• 依托单位: Fujita Gakuen Health University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570406/
• 关键词: Atrioventricular Node; Voltage Clamp; Transient Inward Current; Purkinje fibers; Action Potential; Transient Depolarization; Mexiletine; mexiletine

In order to elucidate the ionic mechanisms of delayed afterdepolarizations, action potential and voltage clamp studies were conducted in canine Purkinje fibers and rabbit atrioventricular node. A transient inward durrent, which was responisble for delayed afterdepolarizations, was obtained on repolarization from various test potentials to -40 - -60 mV under superfusions with 1 m acetylstrophantidin, 0.2 - 1 mM K^+, or 10 m. Ca^<2+> containing Tyrode's solutions, and inhibited by 0.1 mM Cd^<2+> (a Ca^<2+> channel blocker), 5 g/ml mexiletine (a Na^+ channel blocker), or 10 mM caffeine (a Ca^<2+> uptake blocker to sarcoplasmic reticulum). These results suggest that the transient inward current is mediated by a cyclic increase in intracellular Ca^<2+> concentration, and caused by a Ca^<2+> - induced activation of the nonspecific cation channel or a Ca^<2+> -induced activation of Na^+ -Ca^<2+> exchange system. To assess which mechanism is involved, Na^+ concentration in the Tyrode's solution was decreased to 50% of the control (replaced with either Li^+ or sucrose) since extracellular Na^+ does not affect the conductance of the nonspecific cation channel. A transient inward current induced by 0.5 mM K^+ tyrode's solution was then either decreased or inhibited by low Na^+. Next, the effect of 50 M La^<3+> Na^+ -Ca^<2+> exchange blocker) was studied on the transient inward current induced by 092 mM K^+ Tyrode in the presence of 1 mM Cd^<2+>. The transient inward current was again decreased or inhibited by La^<3+>. In conclusion, the results suggest that the transient inward current is induced by an activation of Na^+ -Ca^<2+> exchange system due to an increase in the intracellular Ca^<2+> concentration, and that a Ca^<2+> or a Na^+ channel blocker inhibits the transient inward current by suppressing the Na^+ -Ca^<2+> exchange system as these blockers reduce the intracellular Ca^<2+> or Na^+ overloading by inhibiting the transmembrane influxes of these ions, respectively.

为了阐明延迟后除极的离子机制，在犬浦肯野纤维和家兔房室结上进行了动作电位和电压钳研究。在灌注1 mM乙酰毒毛旋花子苷、0.2 - 1 mM K^+或10 mM时，从各种测试电位复极化至-40 - -60 mV，可获得瞬时内向电流，这是延迟后除极的原因。0.1 mM Cd^<2+>（一种Ca^<2 +>通道阻滞剂）、5 μ g/ml mexilavine（一种Na^+通道阻滞剂）或10 mM咖啡因（一种肌浆网Ca^<2+>摄取阻滞剂）均能抑制这种作用。这些结果表明，瞬时内向电流是由细胞内Ca^<2+>浓度的周期性增加介导的，并由Ca^<2+>诱导的非特异性阳离子通道激活或Ca^<2+>诱导的Na^+ -Ca^<2+>交换系统激活引起。为了评估其中涉及的机制，将台氏液中的Na^+浓度降至对照组的50%（用Li^+或蔗糖代替），因为细胞外Na^+不影响非特异性阳离子通道的电导。然后，低Na^+会降低或抑制由0.5 mM K^+泰罗德溶液诱导的瞬时内向电流。接下来，研究了50 M La^<3+> Na^+ -Ca^<2+>交换阻滞剂）对092 mM K^+台氏液在1 mM Cd^<2+>存在下诱导的瞬时内向电流的影响。La^<3+>可再次降低或抑制瞬时内向电流。上述结果提示，瞬时内向电流是由于细胞内Ca^2+浓度升高，激活Na^+ -Ca^2+交换系统而引起的，Ca^<2+>或Na^+通道阻滞剂通过抑制Na^+ -Ca^<2+>交换系统来抑制瞬时内向电流，因为这些阻滞剂降低了细胞内Ca^<2+>或Na^+超载。

项目成果

渡部良夫、羽渕義純、: 心臓. 19. 770-776 (1987)

渡边吉雄，羽渊吉纯：《心》19. 770-776 (1987)

Watanabe, Y.: Electrophysiology of the Sinoatrial and Atrioventricular Nodes. Alan R. Liss, Inc., 111-131 (1988)

Watanabe，Y.：窦房结和房室结的电生理学。

Watanabe,Y.;Havuch,Y.;Noda,T.;Nishimura,M.: "Cardiac Arrhythmias:Recent Progress in Investigation and Management. Edited by Iwa, T. and Fontaine, G. Abnormal impulse formation in the atrioventricular node. From clinical elec" Elsevier Science Puhblishers

Watanabe，Y.；Havuch，Y.；Noda，T.；Nishimura，M.：“心律失常：调查和管理的最新进展。由 Iwa，T. 和 Fontaine，G 编辑。房室结中的异常冲动形成。

Watanabe.Y,;Habuchi.Y,;Noda.T,;Nishimura.M.: "Cardiac Arrhythmias:Recent Progress in Investigation and Management.Abnormal impulse formation in the atrioventricular node.From clinical electrocardiogram to membrane ionic curre" Elsevier science Publishers

Watanabe.Y,;Habuchi.Y,;Noda.T,;Nishimura.M.：“心律失常：调查和治疗的最新进展。房室结异常脉冲形成。从临床心电图到膜离子电流”Elsevier science Publishers

Watanabe,Y.;Noda,T.;Habuchi,Y.: "Electrophysiology of the Sinoatrial and Atrioventricular Nodes. Edited by Mazgalev, T., Dreifus, L.S. and Michelson, E.L. Effects of cardiac glycosides an AV nodal impulse formati" Alan R.Liss, Inc.,111-131 (1988)

Watanabe,Y.;Noda,T.;Habuchi,Y.：“窦房结和房室结的电生理学。由 Mazgalev, T.、Dreifus, L.S. 和 Michelson, E.L. 编辑。强心苷对 AV 结脉冲格式的影响” Alan R