Figure 1From: Regulation of excitation-contraction coupling in mouse cardiac myocytes: integrative analysis with mathematical modellingSchematic presentation of the components and features of the model. Model accounts for processes that regulate intracellular concentration changes of sodium, potassium and calcium ions. The Ca2+ transport mechanisms are the L-type Ca2+ current (ICa, L), ryanodine receptor (RyR), SR Ca2+ ATPase (SERCA), sarcolemmal Na+/Ca2+ exchanger (NCX), sarcolemmal Ca2+ ATPase (PMCA), and background Ca2+ current (ICa, b). The Ca2+ fluxes within the cell are the uptake of Ca2+ (Jup) from the cytosol to the network sarcoplasmic reticulum (NSR), Ca2+ release (Jrel) from the junctional SR (JSR), Ca2+ flux (Jtr) from the NSR to JSR, Ca2+ leak (Jleak) from the NSR to the cytosol, Ca2+ flux from the subspace (SS) volume to the bulk myoplasm (Jxfer) and from the cytosol to Troponin (JTRPN). The cytosolic bulk Ca2+ concentration is [Ca2+]i. The calcium concentrations in the SS, JSR and NSR compartments are [Ca2+]SS, [Ca2+]JSR and [Ca2+]NSR, respectively. The Ca2+ buffers that operate in the JSR and related to TRPN are presented as CSQN and BUFFER, respectively. The input for the enzyme reactions is the intracellular cytosolic Ca2+ concentration, [Ca2+]i. A rise in the [Ca2+]i level increases Ca2+ binding to calmodulin (CaM), which in turn phosphorylates more Ca2+/calmodulin-dependent protein kinase II (CaMK) and calcineurin (CaN). Phosphorylation of the latter induces phosphorylation of protein phosphatase 1 (PP1). The autophosphorylation of CaMK is presented as a positive feedback loop and PP1 inhibition as a negative feedback. The model also includes the following transmembrane currents: the Ca2+-activated chloride (Cl-) current (ICl, Ca), the rapidly recovering transient outward K+ current (IKto, f), the slow delayed rectifier K+ current (IKs), the rapid delayed rectifier K+ current (IKr), the ultrarapidly activating delayed rectifier K+ current (IKur), noninactivating steady-state voltage activated K+ current (IKss), the time-independent K+ current (IK1), fast Na+ current (INa), Na+ background current (INa, b), and the Na+/K+ pump (INKA).Back to article page