Modelling the integrated regulation role of β-adrenergic signaling and CaMKII in human myocyte electrophysiological properties

Both ß-Adrenergic receptor (ß-AR) signaling pathway and Ca
²⁺
/Calmodulin-dependent protein kinase II (CaMKII) play important roles in regulating cardiac excitation-contraction coupling. However, the laboratory experiments cannot quantify these regulatory roles easily, computer models have been used as an alternative way. The aim of this study was to use computer models to preliminarily investigate the combined role of ß-AR and CaMKII in human cardiac myocyte properties With the hypothesis that the ß-AR is mainly meditated by the targets of protein kinase A (PKA) phosphorylation, the influence of PKA was incorporated into a modified ORd's model. The formulations of L-type Ca
²⁺
current, slow-activating delayed rectifier K
⁺
current and phospholamban were modified. The simulation results were then compared with and without the administration of isoproterenol (ISO). Our simulation showed that, in comparison with the control, at the cycle length of 1000 ms ISO shortened APD90 by 15ms (265 ms vs 250 ms), and the amplitude of Ca
²⁺
transient was increased by approximate 60%. This increase was not observed for [Na
⁺
]. Our findings agreed well with published experimental observations. In conclusion, a computer model has been developed to investigate the role of β-AR and CaMKII in human myocyte electrophysiological properties. This model can be used as a platform to further investigate their role in cardiac arrhythmias.