Relationship between the potassium currents block and the occurrence of early after depolarizations in the setting of sodium current blockade

HYPOTHESIS: We sought to model different degrees blockade of the IKr and IKs in the setting of mild to moderate INa blockade and to study its relationship to the induction of EADs METHODS: We used the cese 1.4.5 platform to run Luo-Rudy Model II of mammalian ventricular action potential. We applied a range of blockade levels to the INa (scaling factor of 50-100%). Then we paced the cell for 5 minutes at a cycle length of 2000 ms to reach steady state before each adjustment of the scaling factors for the IKr or Iks. We adjusted the blockade scale of each current by steps of 1-10% and looked for occurrence of EADs. RESULTS: At each level of blockade of IKs there was a ldquocritical levelrdquo of blockade of IKr after which the EADs started occurring and vice versa. At mild to moderate levels of INa blockade there is a linear relationship between the minimum levels of IKs and IKr blockade at which EADs occur. When INa is blocked, EADs needed lesser degree of potassium currents blockade to occur.