Pathological biomechanical stresses cause cardiac hypertrophy, which is associated with QT prolongation and arrhythmias. Previous studies have demonstrated that repolarizing K+ current densities are decreased in pressure overload-induced left ventricular hypertrophy, resulting in action potential and QT prolongation. Cardiac hypertrophy also occurs with exercise training, but this physiological hypertrophy is not associated with electrical abnormalities or increased arrhythmia risk, suggesting that repolarizing K+ currents are upregulated, in parallel with the increase in myocyte size, to maintain normal cardiac function. To explore this hypothesis directly, electrophysiological recordings were obtained from ventricular myocytes isolated from two mouse models of physiological hypertrophy, one produced by swim-training of wild-type mice and the other by cardiac-specific expression of constitutively active phosphoinositide-3-kinase-p110α (caPI3Kα). Whole-cell voltage-clamp recordings revealed that repolarizing K+ current amplitudes were higher in ventricular myocytes isolated from swim-trained and caPI3Kα, compared with wild-type, animals. The increases in K+ current amplitudes paralleled the observed cellular hypertrophy, resulting in normalized or increased K+ current densities. Electrocardiographic parameters, including QT intervals, as well as ventricular action potential waveforms in swim-trained animals/myocytes were indistinguishable from controls, demonstrating preserved electrical function. Additional experiments revealed that inward Ca2+ current amplitudes/densities were also increased in caPI3Kα, compared with WT, left ventricular myocytes. The expression of transcripts encoding K+, Ca2+ and other ion channel subunits was increased in swim-trained and caPI3Kα ventricles, in parallel with the increase in myocyte size and with the global increases in total cellular RNA expression. In contrast to pathological hypertrophy, therefore, the functional expression of repolarizing K+ (and depolarizing Ca2+) channels is increased with physiological hypertrophy, reflecting upregulation of the underlying ion channel subunit transcripts and resulting in increased current amplitudes and the normalization of current densities and action potential waveforms. Taken together, these results suggest that activation of PI3Kα signalling preserves normal myocardial electrical functioning and could be protective against the increased risk of arrhythmias and sudden death that are prevalent in pathological cardiac hypertrophy.Cardiac hypertrophy is an adaptive response of the heart to increased pressure or volume, and is observed in a variety of cardiac diseases, including in individuals with high blood pressure and/or who have recently experienced a heart attack. This pathological hypertrophy is associated with marked changes in the electrical properties of the heart, predisposing afflicted individuals to life threatening cardiac arrhythmias. Interestingly, hypertrophy is also observed with exercise, particularly in trained athletes, and, in contrast with pathological hypertrophy, physiological hypertrophy is not associated with increased arrhythmia risk. The results presented here demonstrate that ion channel expression is upregulated with exercise and with the activation of metabolic signalling pathways normally triggered by exercise to maintain the normal electrical functioning of the myocardium. These observations suggest that activation of the pathways triggered in physiological hypertrophy may provide a novel therapeutic strategy to reduce or prevent arrhythmias in patients with pathological hypertrophy.