Brain type natriuretic peptide increases L-type Ca2+ current in atrial myocytes by activating natriuretic peptide receptor A

Abstract

Natriuretic peptides are a group of hormones, including atrial-, brain-, and C-type- natriuretic peptides (ANP, BNP, CNP). BNP can bind to two NP receptors (NPRs) denoted NPR-A (activates guanylyl cyclase) and NPR-C (activates inhibitory G- proteins). This study investigated the electrophysiological effects of BNP on isolated mouse atrial myocytes. Current-clamp experiments show that BNP had no effect on action potential (AP) parameters in basal conditions; however, when pre-stimulated with the ?-adrenergic receptor agonist isoproterenol (ISO), BNP prolonged AP duration. Voltage-clamp experiments demonstrate that BNP increased L-type calcium current (ICa,L) in the presence of ISO without altering cardiac potassium currents. The BNP effect on ICa,L was blocked by A71915 (a selective NPR-A antagonist), maintained in myocytes lacking NPR-C receptors and blocked by the phosphodiesterase-3 (PDE-3) inhibitor milrinone. These data demonstrate that BNP prolongs AP duration and increases ICa,L in atrial myocytes by activating NPR-A, increasing intracellular cGMP, and inhibiting PDE- 3.