Iwamoto T, Shigekawa M
Department of Molecular Physiology, National Cardiovascular Center Research Institute, Suita, Osaka 565, Japan.
Am J Physiol. 1998 Aug;275(2):C423-30. doi: 10.1152/ajpcell.1998.275.2.C423.
We compared the properties of three mammalian Na+/Ca2+ exchanger isoforms, NCX1, NCX2, and NCX3, by analyzing the effects of Ni2+ and other cations as well as the recently identified inhibitor isothiourea derivatives on intracellular Na+-dependent 45Ca2+ uptake into CCL-39 (Dede) fibroblasts stably expressing each isoform. All these NCX isoforms had similar affinities for the extracellular transport substrates Ca2+ and Na+. Ni2+ inhibited 45Ca2+ uptake by competing with Ca2+ for the external transport site, with 10-fold less affinity in NCX3 than in NCX1 or NCX2. Ni2+ and Co2+ were most efficient in such discrimination of NCX isoforms, although their inhibitory potencies were less than those of La3+ and Cd2+. The monovalent cation Li+ stimulated 45Ca2+ uptake rate by all NCX isoforms similarly with low affinity, although the extent of stimulation was somewhat smaller in NCX1. On the other hand, the isothiourea derivative KB-R7943 was threefold more inhibitory to NCX3 than to NCX1 or NCX2. Thus distinct differences in the kinetic and pharmacological properties were detected between NCX3 and the other two isoforms.
我们通过分析镍离子（Ni2+）和其他阳离子以及最近发现的抑制剂异硫脲衍生物对稳定表达每种亚型的CCL-39（德德）成纤维细胞内依赖钠离子的45钙离子摄取的影响，比较了三种哺乳动物钠离子/钙离子交换蛋白亚型（NCX1、NCX2和NCX3）的特性。所有这些NCX亚型对细胞外转运底物钙离子和钠离子具有相似的亲和力。Ni2+通过与钙离子竞争外部转运位点来抑制45钙离子摄取，在NCX3中的亲和力比在NCX1或NCX2中低10倍。尽管Ni2+和Co2+的抑制效力低于镧离子（La3+）和镉离子（Cd2+），但它们在区分NCX亚型方面最为有效。单价阳离子锂离子（Li+）以低亲和力类似地刺激所有NCX亚型的45钙离子摄取速率，尽管在NCX1中的刺激程度略小。另一方面，异硫脲衍生物KB-R7943对NCX3的抑制作用比对NCX1或NCX2强三倍。因此，在NCX3与其他两种亚型之间检测到了动力学和药理学特性的明显差异。
