Model simulation in response to changes occurring with aging. Coupled-clock function of adult mice (blue), aged mice when only changes in the M clock mechanisms were taken into account (red), aged mice when only changes in the Ca2+ clock mechanisms were taken into account (yellow), and aged mice when changes in both M and Ca2+ clock mechanisms were included (purple). Membrane voltage, main membrane currents, AC-cAMP-PKA signaling, and Ca2+ cycling (flux and concentration) in the SR in adult and aged mice: membrane voltage (Vm; A); cAMP level (B); PKA activity level (C); flux of Ca2+ existing in the SR (jSRCarel; D); Ca2+ concentration in the junctional SR compartment (CajSR; E); the Na+-Ca2+ exchanger current (INCX; F); HCN current (If; G; L-type current (ICaL; H); and T-type Ca2+ current (ICaT; I).
