Role of sodium-calcium exchanger in modulating the action potential of ventricular myocytes from normal and failing hearts
Role of sodium-calcium exchanger in modulating the action potential of ventricular myocytes from normal and failing hearts
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DOI：
10.1161/01.res.0000080932.98903.d8
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发表时间：
2003-07-11
影响因子：
20.1
通讯作者：
O'Rourke, B
中科院分区：
文献类型：
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作者：
Armoundas, AA;Hobai, IA;O'Rourke, B
心力衰竭和肥厚中 Na+-Ca2+ 交换 (NCX) 活性的增加可以补偿肌浆网状 Ca2+ 摄取的抑制，通过反向模式 Ca2+ 进入提供正性肌力支持，和/或耗尽细胞内 Ca2+ 储存。 NCX 具有产电性，并且依赖于 Na+ 和 Ca2+ 跨膜梯度，因此很难预测其对动作电位 (AP) 的影响。在这里，我们检查了 [Na+](i) 对正常和起搏引起的衰竭犬心脏肌细胞中 AP 的影响，并使用同时记录的 AP 和 Ca2+ 瞬变来估计 NCX 驱动力的方向。 AP 持续时间随着 [Na+](i) 的增加而缩短，并且与 NCX 驱动力反转点的变化相关。当[Na+](i)大于或等于10 mmol/L时，平台期间向外的NCX电流促进复极化，而当[Na+](i)为5 mmol/L时，NCX具有去极化作用，这通过交换抑制肽部分抑制NCX来证实。交换抑制肽在 [Na+](i) 为 5 mmol/L 时缩短 AP 持续时间，在 [Na+](i) 大于或等于 10 mmol/L 时延长 AP 持续时间。当 K+ 电流被阻断时，在 10 mmol/ L [Na+](i) 的 AP 钳位后期平台期间，总膜电流向外，并在接近 NCX 驱动力的预测反转点时变为向内。使用计算机模型再现结果。这些结果表明，NCX 在塑造犬肌细胞的 AP 方面发挥着重要作用，帮助其在高 [Na+](i) 条件下复极化，尤其是在衰竭的心脏中，但在低 [Na+](i) 条件下会产生去极化、潜在致心律失常的影响。
Increased Na+-Ca2+ exchange (NCX) activity in heart failure and hypertrophy may compensate for depressed sarcoplasmic reticular Ca2+ uptake, provide inotropic support through reverse-mode Ca2+ entry, and/or deplete intracellular Ca2+ stores. NCX is electrogenic and depends on Na+ and Ca2+ transmembrane gradients, making it difficult to predict its effect on the action potential (AP). Here, we examine the effect of [Na+](i) on the AP in myocytes from normal and pacing-induced failing canine hearts and estimate the direction of the NCX driving force using simultaneously recorded APs and Ca2+ transients. AP duration shortened with increasing [Na+](i) and was correlated with a shift in the reversal point of the NCX driving force. At [Na+](i) greater than or equal to 10 mmol/ L, outward NCX current during the plateau facilitated repolarization, whereas at 5 mmol/L [Na+](i), NCX had a depolarizing effect, confirmed by partially inhibiting NCX with exchange inhibitory peptide. Exchange inhibitory peptide shortened the AP duration at 5 mmol/ L [Na+](i) and prolonged it at [Na+](i) greater than or equal to 10 mmol/L. With K+ currents blocked, total membrane current was outward during the late plateau of an AP clamp at 10 mmol/ L [Na+](i) and became inward close to the predicted reversal point for the NCX driving force. The results were reproduced using a computer model. These results indicate that NCX plays an important role in shaping the AP of the canine myocyte, helping it to repolarize at high [Na+](i), especially in the failing heart, but contributing a depolarizing, potentially arrhythmogenic, influence at low [Na+](i).