Phospholamban

Phospholamban is a 52 amino acid integral membrane protein that regulates the Ca2+ pump in cardiac muscle cells. Dephosphorylated phospholamban interacts with the Ca2+ ATPase pump (SERCA) to lower its activity and sensitivity to Ca2+, thus decreasing Ca2+ uptake into the sarcoplasmic reticulum (SR). Phospholamban is phosphorylated by Protein Kinase A, inducing an order-to-disorder transition, activating the SERCA. Thus, when phospholamban is phosphorylated, its interaction with SERCA is reduced, resulting in an increase in Ca2+ transport into the SR.

Because phospholamban is a substrate for PKA, which is activated with beta-adrenergic stimulation, one would expect relaxation to be favored when PKA is activated. However, this also means that more Ca2+ is stored in the SR and thus more is available for release; this would increase contractility.

Gene knockout of phospholamban results in animals with hyperdynamic hearts, with little apparent negative consequence.