Effects of the reggae mutation on sinus node function: A simulation study

The sinus node is the primary pacemaker of the heart. A complex interplay of heterogeneities is assumed to be the basic mechanism that the sinus node can drive the heart. This interplay can be disturbed by e.g. diseases, drugs or mutations. In this work the effect of a mutation on the sinus node function were investigated. Therefore, measurement data of wild-type and mutant I_Kr channels were integrated with aid of optimization procedures into the heterogeneous sinus node model of Zhang et al. The measurement data shows a shift of the steady-state inactivation to more positive potentials. Simulated central sinus node cells lose their ability to depolarize spontaneously. Peripheral cell are also effected by the mutation. The main changes are the shortening of the action potential duration from 108 ms to 84 ms and the increase of auto-rhythmic frequency from 6.37 Hz to 7.62 Hz due to an increased mean I_Kr current. In a future study the bradycardial effect of this mutation will be shown in a tissue model.