Electrophysiological effects of the natriuretic peptides BNP and CNP in the sinoatrial node and atrial myocardium

Abstract

Natriuretic peptides (NPs), including ANP, BNP and CNP, constitute a family of hormones that elicit their effects by binding to three receptors denoted NPR-A, NPR-B and NPR-C. The electrophysiological effects of NPs in the heart, particularly in the specialized pacemaker cells of the sinoatrial node (SAN), are poorly understood; therefore, we have investigated the effects of BNP and CNP (10 and 100 nM) on isolated SAN and working atrial myocytes. BNP and CNP increased spontaneous action potential (AP) frequency and increased the slope of the diastolic depolarization in SAN myocytes. Voltage-clamp experiments demonstrate that these effects are the result of increases in the pacemaker current (If) and L-type Ca2+ current (ICa,L). In contrast to SAN myocytes, BNP had no effect on AP parameters in working atrial myocytes under basal conditions. Stimulation of atrial myocytes with isoproterenol (ISO; 10 nM) increased AP duration as well as ICa,L. Application of BNP following prestimulation with ISO further increased atrial myocyte AP duration and ICa,L. The effects of BNP and CNP on SAN myocytes are maintained in mutant mice lacking functional NPR-C receptors. These data suggest that BNP and CNP increase SAN myocyte firing frequency by activating the guanylyl cyclase-linked NPR-A and NPR-B receptors and that the sensitivity of the SAN to NPs is greater than the surrounding working myocardium.