Mean AP firing rate changes in response to drug perturbations. Simulated AP firing rate in absolute numbers (A) and percentage change from the adult basal firing rate (B) of young and adult mouse SAN cells under ISO (1,000 µM), caged cAMP release, or IBMX treatment (3,000 µM). In B, the red bars show the experimental range (defined as mean ± twice the SEM) of the decrease in AP firing rate in aged cells with respect to the adult basal rate, as reported in Larson et al. (2013), Liu et al. (2014), and Sharpe et al. (2017).