FKBP12 is a critical regulator of the heart rhythm and the cardiac voltage-gated sodium current in mice.

ABSTRACT:

Rationale

FK506 binding protein (FKBP)12 is a known cis-trans peptidyl prolyl isomerase and highly expressed in the heart. Its role in regulating postnatal cardiac function remains largely unknown.

Methods and results

We generated FKBP12 overexpressing transgenic (αMyHC-FKBP12) mice and cardiomyocyte-restricted FKBP12 conditional knockout (FKBP12(f/f)/αMyHC-Cre) mice and analyzed their cardiac electrophysiology in vivo and in vitro. A high incidence (38%) of sudden death was found in αMyHC-FKBP12 mice. Surface and ambulatory ECGs documented cardiac conduction defects, which were further confirmed by electric measurements and optical mapping in Langendorff-perfused hearts. αMyHC-FKBP12 hearts had slower action potential upstrokes and longer action potential durations. Whole-c

SUBMITTER: Maruyama M 

PROVIDER: S-EPMC3092589 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature