Cardiomyocyte Membrane Structure and cAMP Compartmentation Produce Anatomical Variation in β₂AR-cAMP Responsiveness in Murine Hearts.

ABSTRACT: Cardiomyocytes from the apex but not the base of the heart increase their contractility in response to β₂-adrenoceptor (β₂AR) stimulation, which may underlie the development of Takotsubo cardiomyopathy. However, both cell types produce comparable cytosolic amounts of the second messenger cAMP. We investigated this discrepancy using nanoscale imaging techniques and found that, structurally, basal cardiomyocytes have more organized membranes (higher T-tubular and caveolar densities). Local membrane microdomain responses measured in isolated basal cardiomyocytes or in whole hearts revealed significantly smaller and more short-lived β₂AR/cAMP signals. Inhibition of PDE4, caveolar disruption by removing cholesterol or genetic deletion of Cav3 eliminated differen

SUBMITTER: Wright PT 

PROVIDER: S-EPMC5912947 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature