Impaired local regulation of ryanodine receptor type 2 by protein phosphatase 1 promotes atrial fibrillation.

ABSTRACT:

Aims

Altered Ca(2+) handling in atrial fibrillation (AF) has been associated with dysregulated protein phosphatase 1 (PP1) and subcellular heterogeneities in protein phosphorylation, but the underlying mechanisms remain unclear. This is due to a lack of investigation into the local, rather than global, regulation of PP1 on different subcellular targets such as ryanodine receptor type 2 (RyR2), especially in AF.

Methods and results

We tested the hypothesis that impaired local regulation of PP1 causes RyR2 hyperphosphorylation thereby promoting AF susceptibility. To specifically disrupt PP1's local regulation of RyR2, we used the spinophilin knockout (Sp(-/-)) mice (Mus musculus) since PP1 is targeted to RyR2 via spinophilin. Without spinophilin, the interaction between PP1 an

SUBMITTER: Chiang DY 

PROVIDER: S-EPMC4133595 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature