Intracellular Na+ concentration is elevated in heart failure but Na/K pump function is unchanged
Intracellular Na+ concentration is elevated in heart failure but Na/K pump function is unchanged
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DOI：
10.1161/01.cir.0000016701.85760.97
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发表时间：
2002-05-28
期刊：
影响因子：
37.8
通讯作者：
Bers, DM
中科院分区：
文献类型：
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作者：
Despa, S;Islam, MA;Bers, DM
细胞内钠浓度（[Na +]（i））通过Na/Ca交换（NCX）调节心脏收缩和电活动。心力衰竭（HF）中NCX的上调可能会放大改变的[Na +]（i）的功能影响。方法和结果-我们通过使用对照和HF兔心室肌细胞（由主动脉瓣关闭不全和收缩引起的HF）中的钠结合苯并呋喃异丁酸酯来测量[Na +]（i）。HF与对照组的静息[Na +]（i）分别为9.7 +/-0.7和6.6 +/-0.5 mmol/L。在这两种情况下，当刺激心肌细胞（0.5 - 3 Hz）时，[Na +]（i）增加约2 mmol/L。为了确定HF中[Na +]（i）升高的机制，我们测量了Na/K泵介导的Na+排出的[Na +]（i）依赖性。V-max（HF和对照组分别为8.3 +/-0.7 vs 8.0 +/-0.8 mmol/L/min）或K-m（分别为9.2 +/-1.0 vs 9.9 +/-0.8 mmol/L）无差异。因此，在测得的[Na +]（i）水平下，HF中的Na/K泵速率实际上更高。然而，HF中静息Na+内流是对照组的2倍（2.3 +/-0.3vs1.1 +/-0.2 mmol/L/min），主要是河豚毒素敏感途径的结果。结论HF中心肌细胞[Na +]（i）升高是由于舒张期Na+内流增加（Na/K-ATP酶特性不变）。在HF中，联合增加[Na +]（i）、减少Ca2+瞬变和延长动作电位深刻影响细胞Ca2+调节，促进动作电位期间通过NCX的更大Ca2+内流。值得注意的是，升高的[Na +]（i）可能是限制HF中观察到的收缩功能障碍的关键。
Background-Intracellular sodium concentration ([Na+](i)) modulates cardiac contractile and electrical activity through Na/Ca exchange (NCX). Upregulation of NCX in heart failure (HF) may magnify the functional impact of altered [Na+](i).Methods and Results-We measured [Na+](i) by using sodium binding benzofuran isophthalate in control and HF rabbit ventricular myocytes (HF induced by aortic insufficiency and constriction). Resting [Na+](i) was 9.7+/-0.7 versus 6.6+/-0.5 mmol/L in HF versus control. In both cases, [Na+](i) increased by approximate to2 mmol/L when myocytes were stimulated (0.5 to 3 Hz). To identify the mechanisms responsible for [Na+](i) elevation in HF, we measured the [Na+](i) dependence of Na/K pump-mediated Na+ extrusion. There was no difference in V-max (8.3+/-0.7 versus 8.0+/-0.8 mmol/L/min) or K-m (9.2+/-1.0 versus 9.9+/-0.8 mmol/L in HF and control, respectively). Therefore, at measured [Na+](i) levels, the Na/K pump rate is actually higher in HF. However, resting Na+ influx was twice as high in HF versus control (2.3+/-0.3 versus 1.1+/-0.2 mmol/L/min), primarily the result of a tetrodotoxin-sensitive pathway.Conclusions-Myocyte [Na+](i) is elevated in HF as a result of higher diastolic Na+ influx (with unaltered Na/K-ATPase characteristics). In HF, the combined increased [Na+](i), decreased Ca2+ transient, and prolonged action potential an profoundly affect cellular Ca2+ regulation, promoting greater Ca2+ influx through NCX during action potentials. Notably, the elevated [Na+](i) may be critical in limiting the contractile dysfunction observed in HF.