Integrating　β-Adrenergic Signaling into a Computational Model of Human Cardiac Electrophysiology

摘要

The sympathetic nervous system influences important cardiac parameters like heart rate, action potential duration (APD) and myocyte contractility. To model its effects on ventricular electrophysiology we integrated an existing description of beta adrenergic signaling pathways into a recent version of the ten Tusscher model of human cardiac electrophysiology. We considered three main target proteins that were phosphory-lated by protein kinase A: the slow delayed potassium channel I_(Ks), the L-type calcium channel I_(Cal) and phospholamban (PLB). Besides shortened APDs we observed a leftward shifted current-voltage relationship of I_(Ks) and an increased channel conductivity. The L-type calcium channel open probability as well as its availability were elevated by the adrenergic stimulation. Due to a reduction of the inhibiting function of PLB on the calcium ATPase, the calcium uptake I_(up) into the sarcoplasmic reticulum was increased. Including intracellular signaling pathways into models of cellular electrophysiology will open new possibilities for the in silico evaluation of physiological and pathological processes. Future work will therefore focus on investigating the influence of adrenergic effects on the tissue and ECG level.