Phospholamban

Phospholamban is a 52 amino acid integral membrane protein that regulates the Ca²⁺ pump in cardiac muscle cells.

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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.

References

• Karim, C. B., T. L. Kirby, Z. Zhang, Y. Nesmelov, and D. D. Thomas. 2004. Phospholamban structural dynamics in lipid bilayers probed by a spin label rigidly coupled to the peptide backbone. Proc Natl Acad Sci USA, 101(40): 14437-14442. Entrez PubMed 15448204

• Brittsan, A. G. & Kranias, E. G. Phospholamban and cardiac contractile function. J. Mol. Cell. Cardiol. 32, 2131-2139 (2000). Entrez PubMed 11112989