Formation of spatially discordant alternans due to fluctuations and diffusion of calcium.
Formation of spatially discordant alternans due to fluctuations and diffusion of calcium.
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DOI：
10.1371/journal.pone.0085365
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Shiferaw Y
中科院分区：
文献类型：
--
作者：
Sato D;Bers DM;Shiferaw Y
动作电位时程的空间不协调交替(SDA)是一种心脏组织不同区域表现出交替的动作电位时程不同序列的现象。SDA是致心律失常的，因为它可以引起不应期的空间异质性，这可能导致波形中断和再入。然而，SDA形成的潜在机制尚不完全清楚。在本文中，我们提出了一种新的形成SDA的机制，在这种情况下，导致交替的细胞不稳定是由细胞内钙循环引起的，并且钙瞬变和动作电位交替在机电上是一致的。特别是，我们证明了当快速起搏的心脏组织由于肌浆网(SR)中的钙积累而发生多次交替时，SDA就形成了。本文提出的机制依赖于观察到的钙循环波动决定了钙交替的相位，因为在起搏早期，钙交替的幅度很小。因此，心肌细胞的不同区域通常会产生钙交替，而在起搏的早期阶段，这种交替是相反的。这些亚细胞模式由于与膜电压的相互作用而逐渐变粗，形成组织尺度上电压和钙的稳态SDA。SDA的这种机制不同于众所周知的依赖于传导速度恢复的机制，以及已知的仅适用于APD和Ca交替机电不协调的情况下的类似图灵的机制。此外，我们认为这一机制是稳健的，很可能是广泛的实验观察到的SDA模式的基础。
Spatially discordant alternans (SDA) of action potential duration (APD) is a phenomenon where different regions of cardiac tissue exhibit an alternating sequence of APD that are out-of-phase. SDA is arrhythmogenic since it can induce spatial heterogeneity of refractoriness, which can cause wavebreak and reentry. However, the underlying mechanisms for the formation of SDA are not completely understood. In this paper, we present a novel mechanism for the formation of SDA in the case where the cellular instability leading to alternans is caused by intracellular calcium (Ca) cycling, and where Ca transient and APD alternans are electromechanically concordant. In particular, we show that SDA is formed when rapidly paced cardiac tissue develops alternans over many beats due to Ca accumulation in the sarcoplasmic reticulum (SR). The mechanism presented here relies on the observation that Ca cycling fluctuations dictate Ca alternans phase since the amplitude of Ca alternans is small during the early stages of pacing. Thus, different regions of a cardiac myocyte will typically develop Ca alternans which are opposite in phase at the early stages of pacing. These subcellular patterns then gradually coarsen due to interactions with membrane voltage to form steady state SDA of voltage and Ca on the tissue scale. This mechanism for SDA is distinct from well-known mechanisms that rely on conduction velocity restitution, and a Turing-like mechanism known to apply only in the case where APD and Ca alternans are electromechanically discordant. Furthermore, we argue that this mechanism is robust, and is likely to underlie a wide range of experimentally observed patterns of SDA.
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影响因子：
20.1
作者：
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DOI：
10.1152/ajpheart.00612.2001
发表时间：
2002-02-01
影响因子：
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作者：
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通讯作者：
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