CHARACTERIZATION OF THE PHOSPHODIESTERASE SUBTYPES THAT REGULATE MOUSE ATRIAL MYOCYTE ELECTROPHYSIOLOGY

Abstract

Phosphodiesterases (PDEs) are the enzymes responsible for the hydrolysis of cyclic nucleotides including cAMP and cGMP. We recently discovered that natriuretic peptides elicit effects in the atrial myocardium via a PDE dependant pathway; however, the role(s) of specific PDE subtypes in atrial myocytes are not clear. Thus, I studied the effects of PDE selective blockers on mouse atrial action potentials (APs) and L-type Ca2+ currents (ICa,L). AP duration (APD) was significantly increased in the presence of IBMX (inhibits all PDEs) as well as EHNA (PDE2 inhibitor) and rolipram (PDE4 inhibitor). The PDE 3 inhibitor milrinone had no effect on APD. Applying milrinone and rolipram (PDE3/PDE4 inhibition) or EHNA, milrinone, and rolipram (PDE2/ PDE3/PDE4 inhibition) in combination prolonged APD as effectively as IBMX. A similar pattern of results was obtained for atrial ICa,L. These data provide novel insight into the unique effects of PDE inhibitors in atrial myocytes