Effects of wildtype and mutant forms of atrial natriuretic peptide on L-type Ca2+ current in mouse atrial myocytes
Atrial natriuretic peptide (ANP) is a hormone with numerous effects in the cardiovascular system, including ion channel physiology. Genetic mapping of a family with hereditary atrial fibrillation (AF) revealed a mutation that produced a mutant ANP (mANP). We used patch-clamping and cAMP assays to investigate the electrophysiological effects of ANP and mANP in mouse atrial myocytes. ANP and mANP had no effects in basal conditions. In the presence of the β-adrenergic receptor agonist isoproterenol (ISO), ANP increased ICa,L density, maximal conductance (Gmax) and hyperpolarized the V1/2 of channel activation (V1/2(act)). ISO and ANP also increased cAMP production. In contrast, ISO+mANP decreased ICa,L density, Gmax and depolarized the V1/2(act) and also decreased cAMP production. ANP’s effects on ICa,L were maintained in NPR-C-/- mice, but absent following NPR-A blockade. mANP effects on ICa,L were lost in NPR-C-/- mice. These opposing effects of ANP and mANP may explain how mANP causes AF.