Ca2+ Sparks and Ca2+ waves are the subcellular events underlying Ca2+ overload during ischemia and reperfusion in perfused intact hearts.
Ca2+ Sparks and Ca2+ waves are the subcellular events underlying Ca2+ overload during ischemia and reperfusion in perfused intact hearts.
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DOI：
10.1016/j.yjmcc.2014.10.011
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发表时间：
2015-02
影响因子：
5
通讯作者：
Escobar, Ariel L.
中科院分区：
文献类型：
--
作者：
Mattiazzi, Alicia;Argenziano, Mariana;Aguilar-Sanchez, Yuriana;Mazzocchi, Gabriela;Escobar, Ariel L.
细胞内 Ca2+ 循环异常在心脏功能障碍中发挥着关键作用，特别是在缺血/再灌注 (I/R) 过程中。缺血期间，胞浆和肌浆网 (SR) Ca2+ 增加。再灌注开始时，胞质 Ca2+ 会出现短暂且突然的增加，这与再灌注心律失常相关。然而，人们对 I/R 期间 Ca2+ 增加的亚细胞动力学知之甚少，并且 SR 作为这种增加背后的机制的可能作用以前被忽视。目前工作的目的是检验两个主要假设： 1. 舒张期 Ca2+ 火花 (cspf) 频率的增加构成缺血引起的舒张期 Ca2+ 增加的主要底物； 2. 胞质 Ca2+ 致心律失常事件（Ca2+ 波）的增加，介导再灌注开始时舒张期 Ca2+ 的突然升高。我们对装载 Fluo-4 的小鼠完整心脏使用共聚焦显微镜。将心脏提交至全局 I/R（12/30 分钟）以评估整个心脏中的心外膜 Ca2+ 火花。完整的心脏火花比分离的心肌细胞更快，而 cspf 则没有不同。缺血期间，cspf 相对于缺血前显着增加（2.07±0.33 vs. 1.13±0.20 sp/sec/100μm，n=29/34，7 颗心脏）。再灌注通过延长 Ca2+ 火花上升时间并降低 cspf 显着改变了 Ca2+ 火花动力学。然而，相对于缺血，它显着增加了 Ca2+ 波频率（0.71±0.14 vs. 0.38±0.06 w/sec/100μm，n=32/33，7 颗心）。结果首次显示了对完整灌注心脏 Ca2+ 火花的评估，并提供了缺血时 Ca2+ 火花增加并在再灌注过程中转化为 Ca2+ 波的直接证据。这些波可能构成再灌注心律失常的主要触发因素。
Abnormal intracellular Ca2+ cycling plays a key role in cardiac dysfunction, particularly during the setting of ischemia/reperfusion (I/R). During ischemia there is an increase in cytosolic and sarcoplasmic reticulum (SR) Ca2+. At the onset of reperfusion there is a transient and abrupt increase in cytosolic Ca2+ which occurs timely associated with reperfusion arrhythmias. However, little is known about the subcellular dynamics of Ca2+ increase during I/R and a possible role of the SR as a mechanism underlying this increase has been previously overlooked. The aim of the present work is to test two main hypotheses: 1. An increase in the frequency of diastolic Ca2+ sparks (cspf) constitutes a mayor substrate for the ischemia-induced diastolic Ca2+ increase; 2. An increase in cytosolic Ca2+ pro-arrhythmogenic events (Ca2+ waves), mediates the abrupt diastolic Ca2+ rise at the onset of reperfusion. We used confocal microscopy on mouse intact hearts loaded with Fluo-4. Hearts were submitted to global I/R (12/30 min) to assess epicardial Ca2+ sparks in the whole heart. Intact heart sparks were faster than in isolated myocytes whereas cspf was not different. During ischemia, cspf significantly increased relative to preischemia (2.07±0.33 vs. 1.13±0.20 sp/sec/100μm, n=29/34, 7 hearts). Reperfusion significantly changed Ca2+ sparks kinetics, by prolonging Ca2+ sparks rise time and decreased cspf. However it significantly increased Ca2+ wave frequency relative to ischemia (0.71±0.14 vs. 0.38±0.06 w/sec/100μm, n=32/33, 7 hearts). The results show for the first time the assessment of intact perfused heart Ca2+ sparks and provides direct evidence of increased Ca2+ sparks in ischemia that transform into Ca2+ waves during reperfusion. These waves may constitute a main trigger of reperfusion arrhythmias.
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影响因子：
20.1
作者：
MANDEL, F;KRANIAS, EG;SCHWARTZ, A
通讯作者：
SCHWARTZ, A
影响因子：
15.9
作者：
MARBAN, E;ROBINSON, SW;WIER, WG
通讯作者：
WIER, WG
影响因子：
37.8
作者：
POGWIZD, SM;CORR, PB
通讯作者：
CORR, PB
影响因子：
5.5
作者：
Dou, Ying;Arlock, Per;Arner, Anders
通讯作者：
Arner, Anders
影响因子：
5
作者：
Escobar, Ariel L.;Perez, Claudia G.;Ramos-Franco, Josefina
通讯作者：
Ramos-Franco, Josefina