| Abstract: |
| Aging of the sinoatrial node (SAN) is associated with progressive alterations in ionic currents and intracellular calcium dynamics, leading to impaired cardiac automaticity. In this study, we investigate the effects of aging at the level of a single pacemaker cell using the Maltsev--Lakatta model, in which rhythmic activity emerges from the interaction between the membrane clock and the calcium clock.
Aging is represented as a gradual modulation of system parameters, in particular a reduction of the $I_f$ current, attenuation of the L-type calcium current ($I_{\mathrm{CaL}}$), and weakening of the coupling between intracellular calcium cycling and the $\mathrm{Na^+}$--$\mathrm{Ca^{2+}}$ exchanger (NCX). Numerical simulations indicate that age-related parameter drift leads to a prolongation of the cycle length, reduced stability of oscillations, and increased sensitivity of the system to perturbations.
The proposed approach provides a foundation for future multiscale analyses. |
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