SERCA, or sarco/endoplasmic reticulum Ca2+-ATPase, is a calcium ATPase-type P-ATPase. It resides in the sarcoplasmic reticulum (SR) in myocytes (see Figure 1) and regulates re-uptake of Ca2+ into the SR. It thereby regulates the contractile properties of muscle cells. Three major paralogs exist:

  • SERCA1
  • SERCA2
  • SERCA3

SERCA2a was identified to specifically regulate the Ca2+ cycling in cardiomyocytes, particularly Ca2+ removal, which triggers myocardial relaxation. SERCA2a is therefore considered a critical factor in the progression of heart failure

Figure 1: Schematic representation of the function of SERCA2a in healthy cardiac myocytes. During diastole, Ca2+ enters the cell (1) and triggers the release of large amounts of Ca2+ from the sarcoplasmic reticulum (SR) (2). This causes the myofilaments to contract (3). At the same time, SERCA2a is released from its inhibitor PLN and shuttles CaCa2+] back into the SR (4), which allows the myofilaments to relax (5).