From beat rate variability in induced pluripotent stem cell-derived pacemaker cells to heart rate variability in human subjects.
From beat rate variability in induced pluripotent stem cell-derived pacemaker cells to heart rate variability in human subjects.
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DOI：
10.1016/j.hrthm.2014.05.037
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发表时间：
2014-10
期刊：
影响因子：
5.5
通讯作者：
Binah, Ofer
中科院分区：
文献类型：
--
作者：
Ben-Ari, Meital;Schick, Revital;Barad, Lili;Novak, Atara;Ben-Ari, Erez;Lorber, Avraham;Itskovitz-Eldor, Joseph;Rosen, Michael R.;Weissman, Amir;Binah, Ofer
关键词：
我们之前报道过，诱导多能干细胞衍生的心肌细胞（iPSC-CM）在人窦房结（SAN）中表现出类似心率变异性（HRV）的心率变异性（BRV）。我们现在假设BRV-HRV连续体起源于起搏器细胞。为了研究细胞BRV是否是HRV动力学的来源，我们假设了不同心肌细胞实体之间的三个水平的相互作用：(1)单个起搏器细胞，(2)电偶联起搏器细胞网络和(3)原位SAN。我们测量了单个起搏器细胞、ipsc衍生的收缩胚状体（EBs）和来自同一个体的心电图的BRV/HRV特性。明显的BRV/HRV在所有三个水平均存在。单细胞间搏间隔（IBI）和poincar<s:1>图SD1和SD2的变异系数（COV）为20 × > EBs (P<0.05)，原位心脏为20 × > EBs（后两者相似，P>0.05）。我们还比较了单个细胞、小细胞（~5-10个细胞）和大细胞（~ 10个细胞）的BRV强度：随着细胞数量的减少，BRV指数逐渐升高（P<0.05）。破坏细胞内Ca2+处理显著增强了BRV的大小，揭示了独特的双峰放电模式，表明细胞内机制有助于BRV/HRV和心律的分形行为。从单细胞到EB的转变过程中，BRV幅度的降低表明原位心脏的HRV起源于多个基于细胞的振荡器的总和和整合。因此，多个起搏器细胞和细胞内Ca2+处理之间的复杂相互作用决定了人类和分离的心肌细胞网络的HRV。
We previously reported that induced Pluripotent Stem Cell-derived cardiomyocytes (iPSC-CM) manifest beat rate variability (BRV) resembling heart rate variability (HRV) in human sinoatrial node (SAN). We now hypothesized the BRV-HRV continuum originates in pacemaker cells. To investigate whether cellular BRV is a source of HRV dynamics, we hypothesized three-levels of interaction among different cardiomyocyte entities: (1) single pacemaker cells, (2) networks of electrically coupled pacemaker cells and (3) in situ SAN. We measured BRV/HRV properties in single pacemaker cells, iPSC-derived contracting embryoid bodies (EBs) and electrocardiograms from the same individual. Pronounced BRV/HRV were present at all three levels. Coefficient of variance (COV) of inter-beat intervals (IBI) and Poincaré plot SD1 and SD2 in single cells were 20x > EBs (P<0.05) and in situ heart (the latter two were similar, P>0.05). We also compared BRV magnitude among single cells, small (~5-10 cells) and larger EBs (>10 cells): BRV indices progressively increased (P<0.05) as cell number decreased. Disrupting intracellular Ca2+ handling markedly augmented BRV magnitude, revealing a unique bi-modal firing pattern, suggesting intracellular mechanisms contribute to BRV/HRV and the fractal behavior of heart rhythm. The decreased BRV magnitude in transitioning from single cell to EB suggests HRV of hearts in situ originates from summation and integration of multiple cell-based oscillators. Hence, complex interactions among multiple pacemaker cells and intracellular Ca2+ handling determine HRV in humans and isolated cardiomyocyte networks.
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影响因子：
37.8
作者：
Mandel Y;Weissman A;Schick R;Barad L;Novak A;Meiry G;Goldberg S;Lorber A;Rosen MR;Itskovitz-Eldor J;Binah O
通讯作者：
Binah O
影响因子：
37.8
作者：
Bigger, JT;Steinman, RC;Cohen, RJ
通讯作者：
Cohen, RJ
影响因子：
7.3
作者：
Hashiatni, Hikaru;Lang, Richard J.;Suzuki, Hikaru
通讯作者：
Suzuki, Hikaru
影响因子：
3.2
作者：
Krstacic, Goran;Parati, Gianfranco;Steiner, Robert
通讯作者：
Steiner, Robert
影响因子：
6
作者：
Kamen, PW;Krum, H;Tonkin, AM
通讯作者：
Tonkin, AM