Simulation of ventricular automaticity induced by reducing inward-rectifier K+ current

Turning non-autonomic ventricular cells into pacemaking cells is believed to hold the key for making a bio-pacemaker that could potentially treat patients with cardiac conduction diseases. In this article, we analyze the effects of various membrane ion channel currents on ventricular automaticity induced by reducing the inward-rectifier K⁺ current (I_K1). It was found that the L-type calcium current (I_CaL), rather than the fast sodium current (I_Na), plays a major role in the rapid depolarization phase of the action potential. With a small I_CaL, the automaticity of cells failed due to incompletion of the rapid depolarization. However, during the slow depolarization phase of the action potential, the background sodium current (I_bNa), background calcium current (I_bCa) and Na⁺/Ca²⁺ exchanger current (I_NaCa) were playing more important roles. In 2D simulations, the automatic ventricular excitations arising from I_K1 reduction only couldn´t propagate; it required other currents to be modulated at the same time for driving the surrounding cardiac tissues.