Wang S-Y, Moczydlowski E, Wang G
Department of Biology, State University of New York at Albany, Albany, NY, USA.
Recept Channels. 2004;10(3-4):131-8. doi: 10.1080/10606820490514914.
After transient transfection of an hNav1.4-L443C/A444W mutant clone, HEK-293 cells exhibited large inactivation-deficient Na+currents. We subsequently established a stable cell line expressing robust inactivation-deficient Na+currents. Persistent late Na+currents were far more sensitive to block by class 1 anti-arrhythmic flecainide, mexiletine, propafenone, and amiodarone at 10 microM than peak Na+currents. Such results support a hypothesis that persistent late Na+currents are in vivo targets for class 1 anti-arrhythmic drugs at their therapeutic plasma concentrations. Stably transfected HEK-293 cells expressing robust inactivation-deficient Na+currents will likely be suitable for screening novel drugs that target persistent late Na+currents selectively.
在瞬时转染hNav1.4-L443C/A444W突变体克隆后，HEK-293细胞表现出大量失活缺陷型Na+电流。随后，我们建立了一个稳定表达强大失活缺陷型Na+电流的细胞系。持续性晚钠电流在10微摩尔时比峰值钠电流对I类抗心律失常药物氟卡尼、美西律、普罗帕酮和胺碘酮的阻断更为敏感。这些结果支持了一个假说，即持续性晚钠电流在其治疗血浆浓度下是I类抗心律失常药物在体内的靶点。稳定转染并表达强大失活缺陷型Na+电流的HEK-293细胞可能适合用于筛选选择性靶向持续性晚钠电流的新型药物。
