Abstract 274: Spatiotemporal Regulation of β Adrenergic Signaling In Heart failure
Our long-term goal is to understand mechanisms that govern spatiotemporal regulation of cAMP/PKA signaling in cardiac myocytes under physiological and pathophysiological conditions, and their implication in cardiac disease therapy. Here we use a series of biosensors to measure cAMP/PKA activity under βAR subtype regulation. In failing cardiac myocytes, the cAMP and PKA activity are shifted from the plasma membrane to the intracellular sarcoplasmic reticulum and the myofilaments. Meanwhile, β2AR displays an increased role in signaling to the myofilaments in failing myocytes when compared to the control myocytes. Moreover, we show that an increased βAR association with phosphodiesterases promotes the alteration in spatiotemporal propagation of cAMP/PKA signaling in failing myocytes. These observations and the underlying mechanisms and functional implications will be discussed.
Author Disclosures: Y.K. Xiang: None F. Barbagallo: None B. Xu: None Q. Fu: None.
This research has received full or partial funding support from the American Heart Association, National Center.
- © 2014 by American Heart Association, Inc.