THE ACTION OF NA+ AS A COFACTOR IN THE INHIBITION BY CYTOPLASMIC PROTONS OF THE CARDIAC NA+-CA2+ EXCHANGER IN THE GUINEA-PIG
THE ACTION OF NA+ AS A COFACTOR IN THE INHIBITION BY CYTOPLASMIC PROTONS OF THE CARDIAC NA+-CA2+ EXCHANGER IN THE GUINEA-PIG
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DOI：
10.1113/jphysiol.1994.sp020336
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发表时间：
1994-10-01
影响因子：
5.5
通讯作者：
LEDERER, WJ
中科院分区：
文献类型：
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作者：
DOERING, AE;LEDERER, WJ
1.在豚鼠心肌肌膜的巨大离体斑片中，通过升高细胞内钠浓度（[Na+]（i））激活Na+-Ca ~（2+）交换电流。当pH（i）同时酸化至6.4时，电流是瞬时的，在30 s内下降80%。预先暴露于pH（i）6.4 15 s可降低Na+-Ca 2+交换电流峰值，而不改变衰减速率或稳态电流。当[Na+]（i）去除9秒时，观察到质子抑制的恢复。Na ~+-Ca ~（2+）交换函数的数学模型再现了实验结果。此外，两个模型依赖的预测实验。(i)Na+-Ca 2+交换的[Na+]（i）依赖性“失活”可能源于pH（i）效应。我们通过实验观察到，预先暴露于酸性pH（i）可以去除归因于[Na+]（i）依赖性“失活”的瞬态电流分量。(ii)酸化应抑制自交换。这一点已被其他缔约方观察到。我们假设细胞内质子对Na+-Ca 2+交换体的抑制有两种成分，其中一种通过增加[Na+]（i）而增强（Doering和Lederer，1993 B）。这一假设是支持这里提出的数据和Na+-Ca 2+交换行为的模型，其中结合细胞内钠的交换增强的亲和力的交换抑制细胞内质子。
1. Na+-Ca2+ exchange current was activated in giant excised patches of guinea-pig cardiac sarcolemma by raising the intracellular sodium concentration ([Na+](i)). When the pH(i) was simultaneously acidified to 6.4, the current was transient, dropping by 80% in 30 s.2. Pre-exposure to a pH(i), of 6.4 for 15 s reduced the peak Na+-Ca2+ exchange current without altering the decay rate or steady-state current. Recovery from proton inhibition was seen when [Na+](i) was removed for 9 s.3. A mathematical model of Na+-Ca2+ exchange function reproduced the experimental results. In addition, two model-dependent predictions were seen experimentally. (i) [Na+](i)-dependent 'inactivation' of Na+-Ca2+ exchange may arise from pH(i) effects. We observed experimentally that pre-exposure to acidic pH(i) can remove the transient current component attributed to [Na+](i)-dependent 'inactivation'. (ii) Self-exchange should be inhibited by acidification. This has been observed by other investigators.4. We have hypothesized that there are two components to inhibition of the Na+-Ca2+ exchanger by intracellular protons, and that one is enhanced by increased [Na+](i) (Doering and Lederer, 1993 b). This hypothesis is supported by the data presented here and by a model of Na+-Ca2+ exchange behaviour in which binding of intracellular sodium to the exchanger enhances the affinity of the exchanger for inhibitory intracellular protons.