Advantages and Limitations of Transgenic Mice: The Role of the Na+/Ca2+ Exchanger in Cardiac Electrophysiology and Arrhythmia

In the search for novel antiarrhythmic strategies, the cardiac Na+/Ca2+ 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 Ca2+ 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.