Improved Ca2+ release synchrony following selective modification of Itof and phase 1 repolarization in normal and failing ventricular myocytes.
Improved Ca2+ release synchrony following selective modification of Itof and phase 1 repolarization in normal and failing ventricular myocytes.
复制标题
在正常和衰竭心室肌细胞中选择性修饰 Itof 和 1 相复极化后，Ca2 释放同步性得到改善。
DOI：
10.1016/j.yjmcc.2022.07.009
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发表时间：
2022
影响因子：
5
通讯作者：
Fowler ED
中科院分区：
文献类型：
--
作者：
Fowler ED
在心力衰竭中，心室动作电位(AP)早期1相复极的丧失可能导致钙离子释放受损，增加心源性猝死的风险。因此，通过增加快速瞬时外向钾电流(ITOF)来恢复AP 1相可能是有益的，但在衰竭的心肌细胞中支持这一命题的直接实验证据是有限的。在正常(豚鼠和兔)和衰竭兔心肌细胞上，用动态钳制技术选择性地调节Itof对AP和Ca~(2+)瞬变的作用。与天然Itofin非衰竭兔心肌细胞相反的是，增加了钙释放的异质性、晚钙放电(LCS)频率和AP持续时间。(警方)。相反，增加Itofin衰竭心肌细胞和豚鼠心肌细胞(后者通常缺乏Itof)可增加钙瞬变幅度、钙释放同步性和缩短时程。计算机模拟还显示，钙瞬变衰减更快(主要是由于LC减少)，内向Na+/Ca~(2+)交换电流和时程下降。当衰竭细胞的Itof电导增加到~0.2nS/pF(这个值略大于典型的人心外膜心肌细胞)时，钙释放同步性提高，AP持续时间略有缩短。Itof的进一步增加可以导致钙释放减少，因为钟形ICa-电压关系的峰值已经过去，AP出现过早的复极化。这些结果表明，存在一个最佳的Itof增强范围，该范围可以支持钙释放的同步性，并改善心力衰竭的电稳定性，但应避免失控的Itof增强。
Loss of ventricular action potential (AP) early phase 1 repolarization may contribute to the impaired Ca2+release and increased risk of sudden cardiac death in heart failure. Therefore, restoring AP phase 1 by augmenting the fast transient outward K+current (Itof) might be beneficial, but direct experimental evidence to support this proposition in failing cardiomyocytes is limited. Dynamic clamp was used to selectively modulate the contribution of Itofto the AP and Ca2+transient in both normal (guinea pig and rabbit) and in failing rabbit cardiac myocytes. Opposing native Itofin non-failing rabbit myocytes increased Ca2+release heterogeneity, late Ca2+sparks (LCS) frequency and AP duration. (APD). In contrast, increasing Itofin failing myocytes and guinea pig myocytes (the latter normally lacking Itof) increased Ca2+transient amplitude, Ca2+release synchrony, and shortened APD. Computer simulations also showed faster Ca2+transient decay (mainly due to fewer LCS), decreased inward Na+/Ca2+exchange current and APD. When the Itofconductance was increased to ~0.2 nS/pF in failing cells (a value slightly greater than seen in typical human epicardial myocytes), Ca2+release synchrony improved and AP duration decreased slightly. Further increases in Itofcan cause Ca2+release to decrease as the peak of the bell-shaped ICa-voltage relationship is passed and premature AP repolarization develops. These results suggest that there is an optimal range for Itofenhancement that may support Ca2+release synchrony and improve electrical stability in heart failure with the caveat that uncontrolled Itofenhancement should be avoided.
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影响因子：
4
作者：
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通讯作者：
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作者：
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影响因子：
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DOI：
10.1152/ajpheart.00748.2003
发表时间：
2004-04-01
影响因子：
4.8
作者：
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通讯作者：
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DOI：
10.1093/europace/euu252
发表时间：
2014
期刊：
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology
影响因子：
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