β-adrenergic stimulation activates early afterdepolarizations transiently via kinetic mismatch of PKA targets

Adrenergic Fight-or-Flight: S-NO Falls on PKA Targets.

Local β-adrenergic stimulation overcomes source-sink mismatch to generate focal arrhythmia.

RATIONALE β-Adrenergic receptor stimulation produces sarcoplasmic reticulum Ca(2+) overload and delayed afterdepolarizations in isolated ventricular myocytes. How delayed afterdepolarizations are synchronized to overcome the source-sink mismatch and produce focal arrhythmia in the intact heart remains unknown. OBJECTIVE To determine whether local β-adrenergic receptor stimulation produces spa...

Inhibition of cAMP-Dependent PKA Activates β2-Adrenergic Receptor Stimulation of Cytosolic Phospholipase A2 via Raf-1/MEK/ERK and IP3-Dependent Ca2+ Signaling in Atrial Myocytes

We previously reported in atrial myocytes that inhibition of cAMP-dependent protein kinase (PKA) by laminin (LMN)-integrin signaling activates β2-adrenergic receptor (β2-AR) stimulation of cytosolic phospholipase A2 (cPLA2). The present study sought to determine the signaling mechanisms by which inhibition of PKA activates β2-AR stimulation of cPLA2. We therefore determined the effects of zinte...

Parathyroid hormone activates TRPV5 via PKA-dependent phosphorylation.

Low extracellular calcium (Ca(2+)) promotes release of parathyroid hormone (PTH), which acts on multiple organs to maintain overall Ca(2+) balance. In the distal part of the nephron, PTH stimulates active Ca(2+) reabsorption via the adenylyl cyclase-cAMP-protein kinase A (PKA) pathway, but the molecular target of this pathway is unknown. The transient receptor potential vanilloid 5 (TRPV5) chan...

Temporal and gefitinib-sensitive regulation of cardiac cytokine expression via chronic β-adrenergic receptor stimulation.

Chronic stimulation of β-adrenergic receptors (βAR) can promote survival signaling via transactivation of epidermal growth factor receptor (EGFR) but ultimately alters cardiac structure and contractility over time, in part via enhanced cytokine signaling. We hypothesized that chronic catecholamine signaling will have a temporal impact on cardiac transcript expression in vivo, in particular cyto...