Increases in Ca2+ influx through Cav1.2 has been observed in cardiovascular disease (CVD) and associated with cardiac arrhythmias. Methods: To mimic the enhanced Cav1.2 activity in CVD, we overexpressed the Cav1.2 β2a subunit in a transgenic mouse model. In-vivo ECGs, ion currents and intracellular Ca2+ were measured in transgenic (TG) and control (CTR) mice. Results: ICaL was greater in TG myocytes (23.9±2.5pA/pF, CTR 13.8±1.6pA/pF). TG mice had enhanced cardiac performance (EF: TG 72.7±1.3%, CTR 66.7±1.5%) but died suddenly (TG 50% vs CTR 100% alive at 6 months), suggesting cardiac arrhythmias. In conscious mice, there was no difference in heart rate in CTR (571±29bpm) and TG (541±24bpm) mice but the QT interval was significantly shorter in TG (44.0±5.5ms, CTR 58.2±3.4ms) mice. Second degree AV block and ectopic premature ventricular beats were observed in all 4 TG mice but not in CTR mice. In anesthetized mice, there was no difference in heart rate (CTR 513±20bpm, TG 526±13bpm) but the PR interval (CTR 32.4±1.4ms, TG 49.8±6.2ms) and QRS duration (CTR 11.4±0.8ms, TG 14.5±0.8ms) were significantly prolonged in TG mice, indicating conduction defects. A significantly greater % of TG myocytes (28.5%) had early (EADs) and delayed (DADs) afterdepolarizations than CTR (0.0%) due to enhanced SR load (caffeine spritz and Fluo-4 F/F0: TG 4.7±0.4 vs. CTR 3.2±0.3) and INCX (TG 2.15±0.6pA/pF vs CTR 1.12±0.3pA/pF at +60mV). However, action potential duration (APD) was significantly shorter in TG myocytes (APD90%: 40.0±5.7ms vs. CTR: 100.6±15.2ms) resulting from an increase of Ito (TG vs. CTR: 60.2±0.8pA/pF vs. 18.7±3.0pA/pF at +50mV). Conclusion: Persistent increases in Ca2+ influx through Cav1.2 cause both conduction disturbances and SR Ca overload, and induce cardiac arrhythmias with shortened APDs and QT intervals.