Altered Na/Ca exchange distribution in ventricular myocytes from failing hearts.
Altered Na/Ca exchange distribution in ventricular myocytes from failing hearts.
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DOI：
10.1152/ajpheart.00597.2015
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发表时间：
2016-01-15
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影响因子：
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通讯作者：
Orchard CH
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作者：
Gadeberg HC;Bryant SM;James AF;Orchard CH
Na/Ca交换（NCX）通常主要位于心室肌细胞的T小管中。然而，NCX的重新分布发生在衰竭心脏的肌细胞中，导致T小管和表面肌膜之间的分布更加均匀;这改变了NCX对肌浆网释放的Ca的通道，从而改变了细胞Ca的处理。在哺乳动物心室肌细胞中，通过Na/Ca交换（NCX）的Ca流出主要发生在T小管。心力衰竭与t管结构破坏有关，但其对t管功能的影响尚不清楚。因此，我们研究了冠状动脉结扎（CAL）或相应的假手术（Sham）后18周从大鼠心脏分离的心室肌细胞中的t-管NCX活性。使用全细胞电压钳技术记录完整和去微管（DT）肌细胞的NCX电流（INCX）和l型Ca电流（伊卡）;使用Fluo-4同时监测细胞内游离Ca浓度（[Ca]i）。INCX被激活，并在应用咖啡因从肌浆网（SR）释放钙的过程中测量。全细胞INCX在Sham和CAL肌细胞中没有显著差异，并且主要发生在Sham肌细胞的T小管中。CAL与INCX和伊卡从T小管到细胞表面的重新分布以及T小管INCX/伊卡密度从假手术中的0.12增加到CAL肌细胞中的0.30相关。CAL肌细胞中t管INCX的减少伴随着SR螯合的Ca分数的增加。然而，SR Ca含量在Sham，Sham DT和CAL肌细胞中没有显著差异，但CAL肌细胞DT显著增加。在Sham心肌细胞中，INCX和[Ca]i之间存在滞后，这在DT Sham中不存在，但在CAL和DT CAL心肌细胞中存在。这些数据表明CAL心肌细胞中NCX的分布改变。
Na/Ca exchange (NCX) is normally located predominantly in the T tubules of cardiac ventricular myocytes. However, redistribution of NCX occurs in myocytes from failing hearts, resulting in more uniform distribution between T tubule and surface sarcolemma; this alters access of NCX to Ca released from sarcoplasmic reticulum and thus cellular Ca handling. In mammalian cardiac ventricular myocytes, Ca efflux via Na/Ca exchange (NCX) occurs predominantly at T tubules. Heart failure is associated with disrupted t-tubular structure, but its effect on t-tubular function is less clear. We therefore investigated t-tubular NCX activity in ventricular myocytes isolated from rat hearts ∼18 wk after coronary artery ligation (CAL) or corresponding sham operation (Sham). NCX current (INCX) and l-type Ca current (ICa) were recorded using the whole cell, voltage-clamp technique in intact and detubulated (DT) myocytes; intracellular free Ca concentration ([Ca]i) was monitored simultaneously using fluo-4. INCX was activated and measured during application of caffeine to release Ca from sarcoplasmic reticulum (SR). Whole cell INCX was not significantly different in Sham and CAL myocytes and occurred predominantly in the T tubules in Sham myocytes. CAL was associated with redistribution of INCX and ICa away from the T tubules to the cell surface and an increase in t-tubular INCX/ICa density from 0.12 in Sham to 0.30 in CAL myocytes. The decrease in t-tubular INCX in CAL myocytes was accompanied by an increase in the fraction of Ca sequestered by SR. However, SR Ca content was not significantly different in Sham, Sham DT, and CAL myocytes but was significantly increased by DT of CAL myocytes. In Sham myocytes, there was hysteresis between INCX and [Ca]i, which was absent in DT Sham but present in CAL and DT CAL myocytes. These data suggest altered distribution of NCX in CAL myocytes.