Division of Clinical and Experimental Electrophysiology, Department of Cardiovascular Medicine, University Hospital Munster, Germany.
Curr Med Chem. 2014;21(11):1330-5. doi: 10.2174/09298673113206660284.
In the search for novel antiarrhythmic strategies, the cardiac Na(+)/Ca(2+) exchanger (NCX) seems to be a promising target. Recent insights into the role of NCX in proarrhythmia stem from transgenic murine models with knockout or overexpression of NCX. There are significant differences regarding cellular electrophysiology, excitation-contraction coupling and Ca(2+) handling when comparing mice to higher mammal and most importantly human physiology. We here review findings derived from transgenic mouse models regarding the role of NCX in the generation of arrhythmia and discuss principle aspects to consider when translating physiological and pathophysiological mechanisms from mouse models into human physiology and the clinical context.
在寻找新的抗心律失常策略的过程中，心脏 Na(+)/Ca(2+) 交换器（NCX）似乎是一个很有前途的靶点。最近对 NCX 在致心律失常中的作用的深入了解源于 NCX 基因敲除或过表达的转基因鼠模型。与高等哺乳动物，尤其是人类生理学相比，当比较小鼠时，细胞电生理学、兴奋-收缩偶联和 Ca(2+) 处理有显著差异。我们在这里回顾了源自转基因小鼠模型的关于 NCX 在心律失常发生中的作用的发现，并讨论了将生理和病理生理机制从小鼠模型转化为人类生理学和临床背景时需要考虑的主要方面。
