Ageing is associated with a decline in cardiac output and a decrease in t-tubular L-type Ca current (ICa), which comprises the trigger for sarcoplasmic reticulum (SR) Ca release, and thus contraction, in ventricular myocytes (1). This decrease in t-tubular ICa is absent in mice that overexpress cardiac caveolin-3 (Cav-3), which appears to localize protein kinase A activity at the t-tubules. We therefore investigated whether cardiac overexpression (OE) of Cav-3 (2) also protects against changes in the systolic Ca transient and its regulation with age. Animal procedures were approved by the local ethics committee and conducted in accordance with UK legislation. Cells isolated from the ventricles of Cav-3 OE and wild type (WT) littermate control mice at 3 or 24 mo of age were field-stimulated at 0.1, 0.2 and 1.0 Hz at room temperature, and intracellular Ca transients monitored using Fluo-4/AM in conjunction with confocal microscopy. β-adrenergic stimulation was provided by 100 nM isoprenaline (ISO). Data were analysed using custom routines written in MATLAB (R2014b) and 2-way repeated measures ANOVA was used for statistical analysis. Fig. 1A shows that WT myocytes had a relatively flat Ca transient amplitude-frequency relationship over the range of stimulation frequencies studied, and that Ca transient amplitude was slightly, but not significantly, smaller at each frequency in the cells from 24 mo compared to 3 mo WT mice. These changes were associated with little change in time to peak (TP) or the time to decay to half maximal amplitude (T50). Fig. 1A also shows that OE had no significant effect on the force-frequency relationship in either age group, nor did it significantly affect TP or T50. In 3 mo WT myocytes, ISO increased Ca transient amplitude by ~74% and TP by ~53%, and decreased T50 by ~30%, but had no significant effect in 3 mo OE myocytes. In contrast, 24 mo WT and OE cells showed a similar response to ISO (Fig. 1B). These data show that the decrease in t-tubular ICa with age is accompanied by only a modest decrease in Ca transient amplitude, and that the effects of Cav-3 on t-tubular ICa density are not reflected in the Ca transient, suggesting that other factors are determining Ca transient amplitude. However, Cav-3 OE may cause age-related changes in the response to β-adrenergic stimulation.