GSK-3β Localizes to the Cardiac Z-Disc to Maintain Length Dependent Activation.

ABSTRACT:

Background

Altered kinase localization is gaining appreciation as a mechanism of cardiovascular disease. Previous work suggests GSK-3β (glycogen synthase kinase 3β) localizes to and regulates contractile function of the myofilament. We aimed to discover GSK-3β's in vivo role in regulating myofilament function, the mechanisms involved, and the translational relevance.

Methods

Inducible cardiomyocyte-specific GSK-3β knockout mice and left ventricular myocardium from nonfailing and failing human hearts were studied.

Results

Skinned cardiomyocytes from knockout mice failed to exhibit calcium sensitization with stretch indicating a loss of length-dependent activation (LDA), the mechanism underlying the Frank-Starling Law. Titin acts as a length sensor for LDA, and knockout

SUBMITTER: Stachowski-Doll MJ 

PROVIDER: S-EPMC8930626 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature