The plateau phase of the ventricular action potential is the result of balanced Ca2+ influx and K+ efflux in cardiac myocytes. The action potential is finally terminated by repolarising K+ currents. Under b-adrenergic stimulation both, the Ca2+-influx and delayed rectifier K+ currents IK are stimulated to maintain cardiac action potential length in a certain range to allow a tightly controlled increase in net Ca2+ influx. The intracellular Ca2+ level is controlled by a Calsequestrin2 (CASQ2) - ryanodine receptor complex, which serves as the most effective Ca2+ store and is located in the sarcoplasmatic reticulum. Here, we study the effects of CASQ2 mutations R33Q, F189L and D307H located in highly conserved regions on the functions of cardiac potassium channels in Xenopus oocytes using two electrode voltage clamp. As a result, CASQ2 wild type and CASQ2-mutants modulate the IKr current, based on the hERG channel. Further, molecular dynamics simulations suggest alterations in the dynamic behavior of the CASQ2-mutants compared to CASQ2 wild type. These in vitro data suggest a regulatory role of CASQ2 for hERG channels which in turn may impact ethiology of Catecholamine-induced Polymorphic Ventricular Tachycardia (CPVT).