Calcium-handling regulatory axis

The calcium-handling regulatory axis is a critical network of proteins that governs the flux of calcium ions (Ca2+) within cardiac myocytes, a process fundamental to excitation-contraction coupling (Source: NIH.gov). Key components of this axis include the ryanodine receptor 2 (RyR2), which mediates Ca2+ release from the sarcoplasmic reticulum (SR); the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2a (SERCA2a), which pumps Ca2+ back into the SR; and phospholamban (PLN), a regulatory protein that inhibits SERCA2a activity (Source: UniProt P16235, P20647). In diseases such as heart failure and various arrhythmias, this axis is often dysfunctional, characterized by reduced SERCA2a activity and 'leaky' RyR2 channels, leading to impaired contractility and increased risk of sudden cardiac death (Source: NIH.gov). Therapeutic strategies targeting this axis aim to restore Ca2+ homeostasis through small molecule modulators, such as RyR2 stabilizers (Rycals) and SERCA2a activators (e.g., istaroxime), or through gene therapy approaches designed to overexpress SERCA2a or inhibit PLN (Source: NIH.gov, FierceBiotech). Additionally, the axis is modulated by signaling pathways involving protein kinase A (PKA) and Ca2+/calmodulin-dependent protein kinase II (CaMKII), which are themselves targets for cardiovascular therapy (Source: ResearchGate).

Other names

Cardiac calcium handling machineryExcitation-contraction coupling axisSERCA2a-PLN-RyR2 axisCalcium handling proteinsS100A1-regulated calcium axis

Modulation of calcium release from and reuptake into the sarcoplasmic reticulum to restore contractile function and electrical stability.