Abstract 11397: PDE4 Controls Basal Cyclic AMP Levels and Beta-Adrenergic Signalling in Human Atrium

Genetic studies have identified SNPs in the gene encoding the type 4D cAMP-specific phosphodiesterase (PDE4D) that confer an increased risk of cardioembolic stroke. Affected individuals were shown to exhibit a lower mRNA expression level for several PDE4D isoforms in their B-lymphocytes. However, the molecular and cellular basis for the association between a reduced PDE4D expression and stroke remains unknown. Because atrial fibrillation (AF) is the most common cause of cardioembolic stroke, we hypothesized that PDE4 inhibition in human atrial muscle might provide a rationale for AF and, in extension, cardioembolic stroke. Here we provide evidence that PDE4 is expressed in human atrial myocytes. PDE4D represents only a small portion of the total PDE activity in human atrium. However, of the four PDE4 subtypes (PDE4A-D), PDE4D is the major form expressed in this tissue. Pharmacological PDE4 inhibition with Ro 20–1724 (Ro, 10 µM) causes an increase in basal L-type Ca2+ channel current, ICa,L. Live cell imag...