Allosteric regulation of Na/Ca exchange current by cytosolic Ca in intact cardiac myocytes.
Allosteric regulation of Na/Ca exchange current by cytosolic Ca in intact cardiac myocytes.
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DOI：
10.1085/jgp.117.2.119
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发表时间：
2001-02
期刊：
影响因子：
--
通讯作者：
Bers DM
中科院分区：
文献类型：
--
作者：
Weber CR;Ginsburg KS;Philipson KD;Shannon TR;Bers DM
心肌肌层Na-Ca交换器（NCX）受[Ca]i的变构调节，当[Ca]i低时，NCX电流（INCX）失活。在这项研究中，我们使用膜电位（Em）和INCX来控制完整心肌细胞的钙进入和钙外排，以研究这种变构调节（钙激活）是否在生理范围内发生。在没有Ca活化的情况下，增加[Ca]i的电化学效应将是增加向内的INCX （Ca外排）和减少向外的INCX。另一方面，Ca活化会在两个方向上增加INCX。因此，我们将[Ca]i依赖性外展INCX的增加归因于变构调节。在雪貂肌细胞中观察到Ca对INCX的激活，而在野生型小鼠肌细胞中没有观察到，这表明Ca对NCX的调节可能是物种依赖的。我们还研究了过表达正常犬NCX或缺乏钙调节的犬NCX的转基因小鼠肌细胞（Δ680-685）。携带正常犬NCX基因的动物显示Ca激活，而携带突变基因的动物则没有，证实了该区域在这一过程中的作用。在天然雪貂细胞和表达犬类NCX的小鼠中，Ca在生理条件下进行变构调节（KmCaAct = 125±16 nM SEM≈静息[Ca]i）。这一点，再加上在我们的条件下，在测量到的[Ca]i和INCX激活之间没有观察到延迟，表明NCX功能的搏动变化可以在体内发生。INCX激活状态的这些变化可能会影响SR钙负荷和静息[Ca]i，有助于在正常和病理生理条件下微调细胞内钙的流入和流出。我们未能在小鼠肌细胞中观察到Ca活化，可能是由于Ca调节的程度或KmCaAct与其他物种的差异。我们对KmCaAct的估计基于Ca活化的模型预测，证实Ca活化强烈影响向外INCX，这解释了为什么它会随着[Ca]i的增加而增加而不是下降。
The cardiac sarcolemmal Na-Ca exchanger (NCX) is allosterically regulated by [Ca]i such that when [Ca]i is low, NCX current (INCX) deactivates. In this study, we used membrane potential (Em) and INCX to control Ca entry into and Ca efflux from intact cardiac myocytes to investigate whether this allosteric regulation (Ca activation) occurs with [Ca]i in the physiological range. In the absence of Ca activation, the electrochemical effect of increasing [Ca]i would be to increase inward INCX (Ca efflux) and to decrease outward INCX. On the other hand, Ca activation would increase INCX in both directions. Thus, we attributed [Ca]i-dependent increases in outward INCX to allosteric regulation. Ca activation of INCX was observed in ferret myocytes but not in wild-type mouse myocytes, suggesting that Ca regulation of NCX may be species dependent. We also studied transgenic mouse myocytes overexpressing either normal canine NCX or this same canine NCX lacking Ca regulation (Δ680–685). Animals with the normal canine NCX transgene showed Ca activation, whereas animals with the mutant transgene did not, confirming the role of this region in the process. In native ferret cells and in mice with expressed canine NCX, allosteric regulation by Ca occurs under physiological conditions (KmCaAct = 125 ± 16 nM SEM ≈ resting [Ca]i). This, along with the observation that no delay was observed between measured [Ca]i and activation of INCX under our conditions, suggests that beat to beat changes in NCX function can occur in vivo. These changes in the INCX activation state may influence SR Ca load and resting [Ca]i, helping to fine tune Ca influx and efflux from cells under both normal and pathophysiological conditions. Our failure to observe Ca activation in mouse myocytes may be due to either the extent of Ca regulation or to a difference in KmCaAct from other species. Model predictions for Ca activation, on which our estimates of KmCaAct are based, confirm that Ca activation strongly influences outward INCX, explaining why it increases rather than declines with increasing [Ca]i.
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影响因子：
5.5
作者：
LIPP, P;POTT, L
通讯作者：
POTT, L
影响因子：
20.1
作者：
HAWORTH, RA;GOKNUR, AB
通讯作者：
GOKNUR, AB
影响因子：
2.9
作者：
Baazov, D;Wang, XL;Khananshvili, D
通讯作者：
Khananshvili, D
心脏钠钙交换的稳态和动态特性。细胞质钙和ATP的次要调节。
DOI：
10.1085/jgp.100.6.933
发表时间：
1992-12
期刊：
The Journal of general physiology
影响因子：
--
作者：
Hilgemann DW;Collins A;Matsuoka S
通讯作者：
Matsuoka S
影响因子：
3.8
作者：
Ginsburg, KS;Wieber, CR;Bers, DM
通讯作者：
Bers, DM