Role of Abnormal Intracellular Calcium Dynamics in the genesis of electrical alternans in the heart

细胞内钙动态异常在心脏电交替发生中的作用

• 批准号: 18590784
• 负责人: TANAKA Hideo
• 金额: $ 2.39万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590784/
• 关键词: cardiomvoc; calcium ion; electrical alternans; arrhythmia; confocal microscopy; sarcoplasmic reticulum; Va-Ca exchange

This study was designed to clarify the role of intracellular calcium dynamics in the electrical alternans; a clinically useful indicator for the development of fatal ventricular tachyarrhythmias. By applying a dual-view, rapid scanning confocal microscopy for simultaneous detection of both the intracellular calcium dynamics and the corresponding membrane potentials to Langendorff-perfused rat hearts, we conducted confocal imaging of the fluo4- and RH237-signals at cellular levels. With this novel approach, following results were obtained.1. We succeeded in detecting both the intracellular calcium dynamics and membrane potentials simultaneously in the perfused rat heart.2. Under atrio-ventricular conduction block, individual myocytes exhibited calcium waves sporadically with no discernible membrane depolarization.3. Under low K perfusion with isoproterenol, burst pacing of the heart resulted in genesis of triggered activity and subsequent calcium oscillation mediated by calcium waves that were accompanied by membrane oscillation.4. Such calcium wave-mediated oscillatory membrane potentials were attenuated by ryanodine and SEA0400, a blocker for Na-Ca exchange.5. Reduced calcium release from the sarcoplasmic reticulum, by ryanodine failed to evoke calcium alternans. However, high-frequency pacing of the heart at 4-5 Hz resulted in development of calcium alternans, whereas the individual myocytes showed no beat-to-beat alternans of action potential waveforms.In summary the present results indicate an essential role of calcium waves in the genesis of triggered activity. On the other hands, calcium alternans evoked presumably by depressed calcium release function were not accompanied by electrical alternans, suggesting that electrical alternans is not responsible for the cellular heterogeneity of calcium handings, but regional heterogeneity in the heart.

本研究旨在阐明细胞内钙动力学在电交替中的作用；致命性室性快速心律失常发生的临床有用指标。通过应用双视图快速扫描共焦显微镜同时检测 Langendorff 灌注大鼠心脏的细胞内钙动态和相应的膜电位，我们在细胞水平上对 Fluo4 和 RH237 信号进行了共聚焦成像。采用这种新颖的方法，得到了以下结果： 1．我们成功地同时检测了灌注大鼠心脏的细胞内钙动态和膜电位。 2．房室传导阻滞时，个别肌细胞偶见钙波，无明显膜去极化。3．在异丙肾上腺素低钾灌注下，心脏突发起搏导致触发活动的发生，随后钙波介导钙振荡，并伴有膜振荡。 4．这种钙波介导的振荡膜电位被兰尼定和 SEA0400（Na-Ca 交换阻断剂）减弱。5．兰尼定减少了肌浆网的钙释放，但未能引起钙交替。然而，4-5 Hz 的高频心脏起搏导致钙交替的发生，而单个肌细胞没有表现出动作电位波形的逐搏交替。 总之，目前的结果表明钙波的重要作用在触发活动的起源中。另一方面，可能由钙释放功能抑制引起的钙交替症并不伴随电交替症，这表明电交替症不是钙处理的细胞异质性的原因，而是心脏中的区域异质性的原因。

项目成果

Single-cell imaing of living organs

活体器官的单细胞成像

• 发表时间: 2007
• 作者: Tanaka H;Takamatsu T
• 通讯作者: Takamatsu T

Role of intracellular calcium waves in triggered arrhythmias -simultaneous confocal recording of single-cell membrane potentials and calcium dynamics in the rat heart-

细胞内钙波在触发心律失常中的作用-同时共聚焦记录大鼠心脏中的单细胞膜电位和钙动态-

• 发表时间: 2007
• 作者: Tanaka H;Fujiwara K;Nakagami T;Maui H;Oyamada M;Takamatsu T;Tanaka H
• 通讯作者: Tanaka H

ニポウディスク法 染色・バイオイメージング実験ハンドブック

Nippow圆盘法染色/生物成像实验手册

• 发表时间: 2006
• 作者: 藤原克次;田中秀央;高松哲郎
• 通讯作者: 高松哲郎

Nipkow disc scanning

Nipkow 光盘扫描

• 发表时间: 2006
• 期刊: Handbook of Staining and Bioimaging (Youdosha)
• 作者: Fujiwara;K.;Tanaka;H.;Takamatsu;T
• 通讯作者: T

Enhanced activity of ventricular Na^+-HCO_3^- cotransport ure-overload hypertrophy.

心室Na^-HCO_3^-共转运尿素超负荷肥厚活性增强。

• 发表时间: 2007
• 期刊: Am J Physiol Heart Circ Physiol 293(in press)
• 作者: Tanaka;H.;Oyamada;M.;Tsujii;E.;Mani;H.;Nakagami;T.;Fujiwara;K.;Takamatsu;T;Dai P;Yamamoto T
• 通讯作者: Yamamoto T