Development of a biophysically detailed model of the rapid-delayed rectifier potassium channel

The human ether-à-go-go-related-gene (hERG) encodes potassium channels responsible for the rapid delayed rectifier current I_Kr, which plays a critical role in the repolarisation of cardiac action potentials. hERG/I_K. channel mutations result in defective repolarisation, which may lead to life-threatening conditions such as the long and short QT syndromes. To study the functional consequences of impaired hERG/Iκr channel on arrhythmogenesis, we developed a Markov chain model of hERG current (I_hERG) that accurately reproduces the characteristics of normal and aberrant hERG/I_Kr during cardiac action potential waveforms. The model was validated by comparing simulated results from different voltage clamp protocols against experimental data. The model accommodates alterations that reproduce changes to I_hERG.