Experimental arrhythmia model and computer simulated action potential study on Andersen syndrome

Andersen syndrome (LQT7) is a rare disorder characterized by periodic paralysis and ventricular arrhythmias (VA). It has been reported the mutation of Kir2.1 (inwardly rectifying potassium current: IK1) causes loss of function and results in this syndrome. We examined the relationship between the inhibition of Kir2 and VA. Action potentials and IK1 were recorded from guinea-pig isolated ventricular myocytes using the voltage or current-clamp method. Ba2+ (1mM) inhibited IK1 by 91% and induced unstability of the resting potential, which finally induced triggered activity. In a computer-simulated action potential using the Luo and Rudy model, the reduction of IK1 by 90% induced abnormal automaticity, mimicking the experimental results. There was a critical reduction of IK1 to induced the automaticity. When the reduction was less than by 72%, no automaticity appeared, but when it was more than by 73% automaticity started abruptly. The mechanism of ventricular arrhythmias in LQT7 may be triggered activity and the critical reduction may be important for the initiation of VA.