Inducible polymorphic ventricular tachyarrhythmias in a transgenic mouse model with a long Q-T phenotype

We created a mouse model with a prolonged Q-T interval and spontaneous arrh ythmias by overexpressing the NH2 terminus and first transmembrane segment (Kv1.1N206Tag) of a delayed rectifier potassium channel (LQT(+/-) mouse). A nalyses were performed using whole cell recordings of cardiac myocytes, sur face electrocardiography, and programmed electrical stimulation. Action pot ential duration (APD) was prolonged to the same extent and was more highly variable in myocytes derived from LQT(+/-) and LQT(+/+) mice than in myocyt es derived from wild-type (WT) FVB mice. Under ketamine anesthesia, the Q-T interval of both LQT(+/+) and LQT(+/-) mice was comparably prolonged versu s that of WT mice. Stimulation of the right ventricle using an intracardiac catheter induced polymorphic ventricular tachyarrhythmias in 50% of the LQ T(+/-) mice and 36% of the LQT(+/+) mice, whereas polymorphic ventricular t achyarrhythmias were not inducible in WT mice. The analyses of LQT(+/-) and LQT(+/+) mice indicate that prolongation of the Q-T interval in LQT mice i s associated with prolonged APD, increased dispersion of APD among cardiocy tes, and inducibility of polymorphic ventricular tachycardia, providing the substrate for spontaneous arrhythmias in these animals.