Interplay of potassium channels in modulating the action potential of the human left ventricle

The interplay of potassium ion channels in modulating the action potential (AP) of the human left ventricle has not been well elucidated due to the precise nature of some underlying ionic components that are not fully characterized. In the current study, we have developed an allosteric conformation model for rapid delayed rectifier (IKr) and incorporated this into the ten Tusscher´s model for human ventricular myocytes. The transmural densities of IKr, the slow delayed rectifier (IKs) and the transient outward channel (Ito) were refined based on the variable expression of the underlying protein subunits. Our results demonstrated that the modified model was able to reproduce an AP duration (APD) of 313 ms in Epi, 349 ms in M and 300 ms in Endo at 1 Hz pacing. A frequency change from 1 Hz to 0.5 Hz resulted in an APD difference of 20 ms for Epi, 32 ms for M and 20 ms for Endo. Ito effected the early phase of AP, however, had no significant influence on APD. An increase of IKr progressively suppressed IKs in Epi and Endo, however, caused a paradoxical change of IKs in M cells. In summary, our results have suggested a coincident decrease of IKs with excessive decrease of IKr in M cells would be a substrate of their high susceptibility to APD prolongation.