Fig. 1.

Development of delayed afterdepolarizations (DADs) in a mathematical model (Noble98). Top to bottom: Ca²⁺current through ryanodine receptors (RyRs; A), current through the Na⁺/Ca²⁺ exchanger (NCX; B), cell membrane potential (voltage; C), and L-type Ca²⁺ current (I_CaL; D). Shown is the Noble98 model under Na⁺ overload, which was found to produce Ca²⁺ oscillations and DADs (see text). The first action potential (AP; at 0.1 s) was produced as a result of stimulus current (after 1-Hz pacing), whereas the following depolarizations occurred as a result of Ca²⁺ release, where RyRs were activated by the increased Ca²⁺ within the cell. Note that the first and third DADs were not accompanied by enough membrane depolarization to activate fast Na⁺ current and I_CaL, whereas the second and fourth DADs did (see differences in NCX), thereby producing full APs.