Figure 8

Computational simulation of Na-dependence of SN pacemaking by using the Maltsev–Lakatta minimal model¹⁴ in the presence (blue traces) and in the absence (brown traces) of reverse NCX. Brown traces represent NCX function when only the forward (negative current) mode was active. Intracellular Na⁺-concentration was changed from 2 to 10 mM (vertical columns) and the behaviour of the action potential (panel a first row), NCX-current (panel a second row), global intracellular Ca²⁺ (panel a third row), SR Ca²⁺ content (panel a fourth row) and I_CaL (panel a last row) were investigated. In the presence of reverse NCX (blue curves), increase of Na⁺_i enhances SN pacemaking with parallel increase of outward NCX and network SR Ca²⁺ content. In the absence of reverse mode, the SN pacemaking failed at all Na⁺_i levels (panel a) and a considerable loss in the SR Ca²⁺ content was observed.