Beat-to-beat repolarization variability in ventricular myocytes and its suppression by electrical coupling.
Beat-to-beat repolarization variability in ventricular myocytes and its suppression by electrical coupling.
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DOI：
10.1152/ajpheart.2000.278.3.h677
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发表时间：
2000-03
期刊：
影响因子：
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通讯作者：
M. Zaniboni;Andrew E. Pollard;Lin Yang;K. Spitzer
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文献类型：
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作者：
M. Zaniboni;Andrew E. Pollard;Lin Yang;K. Spitzer
以恒定速率起搏并保持在恒定温度下的单个心室肌细胞表现出动作电位时程（APD）的逐搏变化。在这项研究中，我们试图量化这种变异性，评估其机制，并确定其与另一个肌细胞的电紧张相互作用的反应。单个细胞搏间APD（90）（90%复极）呈正态分布。因此，我们将APD（90）变异性定量为变异系数，CV =（SD/平均APD（90））× 100。正常溶液中CV的平均值± SD为2.3 ± 0.9（132个细胞）。细胞外TTX（13 μ M）和细胞内EGTA（14 mM）均显著降低CV分别为44%和26%。当组合应用时，CV下降了54%。相反，L-691，121（100 nM）抑制快速延迟整流电流使CV增加300%。当两个正常心肌细胞以100 MOmega的连接电阻（R（j））电连接时，CV也显著降低35%。电耦合（R（j）= 100 MOmega）的正常心肌细胞的一个产生早期后去极化（EAD）完全阻断EAD的形成。这些结果表明，心跳到心跳APD的变异性可能是介导的随机行为的离子通道和电紧张性的相互作用，以限制时间分散的不应期，一个主要的贡献者emmogenesis。
Single ventricular myocytes paced at a constant rate and held at a constant temperature exhibit beat-to-beat variations in action potential duration (APD). In this study we sought to quantify this variability, assess its mechanism, and determine its responsiveness to electrotonic interactions with another myocyte. Interbeat APD(90) (90% repolarization) of single cells was normally distributed. We thus quantified APD(90) variability as the coefficient of variability, CV = (SD/mean APD(90)) x 100. The mean +/- SD of the CV in normal solution was 2.3 +/- 0.9 (132 cells). Extracellular TTX (13 microM) and intracellular EGTA (14 mM) both significantly reduced the CV by 44 and 26%, respectively. When applied in combination the CV fell by 54%. In contrast, inhibition of the rapid delayed rectifier current with L-691,121 (100 nM) increased the CV by 300%. The CV was also significantly reduced by 35% when two normal myocytes were electrically connected with a junctional resistance (R(j)) of 100 MOmega. Electrical coupling (R(j) = 100 MOmega) of a normal myocyte to one producing early afterdepolarization (EAD) completely blocked EAD formation. These results indicate that beat-to-beat APD variability is likely mediated by stochastic behavior of ion channels and that electrotonic interactions act to limit temporal dispersion of refractoriness, a major contributor to arrhythmogenesis.