Rate dependence of the INa-IKI complex on human ventricular conduction velocity under hypokalemia and hyperkalemia conditions

摘要

Conduction velocity (CV) heterogeneities are a long established pro-arrhythmic substrate in cardiac disease, including atrial fibrillation and cardiomyopathies. One mechanism for generating dispersion of electrical conduction is conduction slowing in myocardial tissue. The rate dependent interactions of the I_no-I_ki ion channel complex on human ventricular CV are studied using an in-silico model. Two response domains of myocardial tissue are found. There exists a slow frequency of pacing domain (1 Hz), where CV is largely governed by the I_Na channel alone. In the fast frequency domain (3.3 Hz), I_K1 plays a more dominant role in ventricular CV. The simulation results suggest that, under arrhythmogenic conditions, the upper limit of the CV is governed by the fast sodium to inwardly rectifying potassium channel conductivity ratio. The role of these two channels in determining the CV is further investigated under hypokalemic and hyperkalemic conditions. A marked decrease in human ventricular CV during mild hyperkalemia and a bi-phasic response during a hypokalemic episode were found. Additionally, I_K1 is found to lose its role in governing CV under severe hypokalemic conditions, whilst I_Na channel conductivity is found to be crucial in all the considered scenarios.