Terracciano C M, Hancox J C
National Heart and Lung Institute, Hammersmith Campus, Imperial College London, London, UK.
Br J Pharmacol. 2013 Oct;170(4):765-7. doi: 10.1111/bph.12299.
The sodium-calcium exchanger (NCX) is an electrogenic transporter that is widely expressed in different tissues. In the heart, the NCX plays important roles in calcium ion homeostasis, excitation-contraction coupling and the electrophysiological properties of cardiac myocytes. Precise determination of the roles of the NCX has somewhat been hampered by a lack of selective small molecule inhibitors. In this issue of the BJP, Jost and colleagues present data on a new NCX inhibitor, ORM-10103, which has submicromolar EC50 values against cardiac forward and reverse exchange activity. The compound exhibits improved selectivity over existing small molecule NCX inhibitors and, in particular, appears to be without effect on L-type calcium channels at high concentrations. ORM-10103 could therefore have significant value for studies of the (patho)physiological roles of the NCX in the heart. Further pharmacological studies are required to investigate the actions of ORM-10103 on cardiac cells and tissues and to determine its effects on non-cardiac NCX isoforms.
钠钙交换体（NCX）是一种生电转运体，在不同组织中广泛表达。在心脏中，NCX在钙离子稳态、兴奋-收缩偶联以及心肌细胞的电生理特性方面发挥着重要作用。由于缺乏选择性小分子抑制剂，对NCX作用的精确测定在一定程度上受到了阻碍。在本期《英国药理学杂志》中，约斯特及其同事展示了一种新型NCX抑制剂ORM-10103的数据，该抑制剂对心脏正向和反向交换活性的半数有效浓度（EC50）值处于亚微摩尔水平。与现有的小分子NCX抑制剂相比，该化合物表现出更高的选择性，特别是在高浓度时似乎对L型钙通道没有影响。因此，ORM-10103对于研究NCX在心脏中的（病理）生理作用可能具有重要价值。需要进一步的药理学研究来探究ORM-10103对心脏细胞和组织的作用，并确定其对非心脏NCX亚型的影响。
