Phospholamban pentamerization increases sensitivity and dynamic range of cardiac relaxation.

ABSTRACT:

Aims

A key event in the regulation of cardiac contraction and relaxation is the phosphorylation of phospholamban (PLN) that relieves the inhibition of the sarco/endoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a). PLN exists in an equilibrium between monomers and pentamers. While only monomers can inhibit SERCA2a by direct interaction, the functional role of pentamers is still unclear. This study investigates the functional consequences of PLN pentamerization.

Methods and results

We generated transgenic mouse models expressing either a PLN mutant that cannot form pentamers (TgAFA-PLN) or wild-type PLN (TgPLN) in a PLN-deficient background. TgAFA-PLN hearts demonstrated three-fold stronger phosphorylation of monomeric PLN, accelerated Ca2+ cycling of cardiomyocytes, and enhanced

SUBMITTER: Funk F 

PROVIDER: S-EPMC10318394 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature