We tested the hypothesis that chronic changes in intracellular Ca²⁺ (Ca²⁺_i) can result in changes in ion channel expression; this represents a novel mechanism of crosstalk between changes in Ca²⁺ cycling proteins and the cardiac action potential (AP) profile. We used a transgenic mouse with cardiac‐specific overexpression of sarcoplasmic reticulum Ca²⁺ ATPase (SERCA) isoform 1a (SERCA1a OE) with a significant alteration of SERCA protein levels without cardiac hypertrophy or failure. Here, we report significant changes in the expression of a transient outward K⁺ current (I_to,f), a slowly inactivating K⁺ current (I_K,slow) and the steady state current (I_SS) in the transgenic mice with resultant prolongation in cardiac action potential duration (APD) compared with the wild‐type littermates. In addition, there was a significant prolongation of the QT interval on surface electrocardiograms in SERCA1a OE mice. The electrophysiological changes, which correlated with changes in Ca²⁺_i, were further corroborated by measuring the levels of ion channel protein expression. To recapitulate the in vivo experiments, the effects of changes in Ca²⁺_i on ion channel expression were further tested in cultured adult and neonatal mouse cardiac myocytes. We conclude that a primary defect in Ca²⁺ handling proteins without cardiac hypertrophy or failure may produce profound changes in K⁺ channel expression and activity as well as cardiac AP.