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Figure 1 | BMC Physiology

Figure 1

From: Regulation of excitation-contraction coupling in mouse cardiac myocytes: integrative analysis with mathematical modelling

Figure 1

Schematic 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).

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