Inhibition of L-type Ca²⁺current by C-type natriuretic peptide in bullfrog atrial myocytes: an NPR-C-mediated effect

Abstract

Single atrial myocytes were isolated from the bullfrog heart and studied under current and voltage clamp conditions to determine the electrophysiological effects of the C-type natriuretic peptide (CNP). CNP (10(-8) M) significantly shortened the action potential and reduced its peak amplitude after the application of isoproteronol (10(-7) M). In voltage clamp studies, CNP inhibited isoproteronol-stimulated L-type Ca2+ current (ICa) without any significant effect on the inward rectifier K+ current. The effects of cANF (10(-8) M), a selective agonist of the natriuretic peptide C receptor (NPR-C), were very similar to those of CNP. Moreover, HS-142-1, an antagonist of the guanylyl cyclase-linked NPR-A and NPR-B receptors did not alter the inhibitory effect of CNP on ICa. Inclusion of cAMP in the recording pipette to stimulate ICa at a point downstream from adenylyl cyclase increased ICa, but this effect was not inhibited by cANF. These results provide the first demonstration that CNP can inhibit ICa after binding to NPR-C, and suggest that this inhibition involves a decrease in adenylyl cyclase activity, which leads to reduced intracellular levels of cAMP.

Functional characterization of cardiac progenitor cells and their derivatives in the embryonic heart post‐chamber formation

“…Indeed, the E11 ventricular myocardium has been shown to express high levels of NOS and cGMP proteins compared to the E16 myocardium (Ji et al, 1999) and also to respond to muscarinic and adrenergic stimulation . Activation of NPR-C was shown to significantly inhibit ISO induced Ltype Ca 2þ current (LTCC) via the Gi pathway in adult SA nodal, atrial, and ventricular myocytes (Rose et al, 2003(Rose et al, , 2004(Rose et al, , 2005 (Fig. 7A).…”

Effects of Wild-Type and Mutant Forms of Atrial Natriuretic Peptide on Atrial Electrophysiology and Arrhythmogenesis

“…These measurements demonstrate that neither ANP nor mANP had any effects on mouse atrial AP properties in basal conditions (Figure IB and Tables II and III in the Data Supplement). Because we have previously shown that I Ca,L is a major target of NPs in the atria, 13,15 we also measured the effects of ANP and mANP (100 nmol/L doses) on basal I Ca,L in mouse right atrial myocytes ( Figure IC The absence of effects of ANP on AP morphology and I Ca,L in basal conditions is consistent with our previous studies showing that the related peptides BNP and CNP only affect mouse atrial myocyte electrophysiology in the presence of the β-adrenergic receptor agonist isoproterenol. 13 Accordingly, we next measured the effects of ANP and mANP on AP morphology in mouse atrial myocytes after application of isoproterenol (10 nmol/L).…”

“…10 We have recently demonstrated that NPs have potent effects on cardiac electrophysiology. [13][14][15][16] For example, BNP and CNP can increase action potential (AP) duration (APD) in association with increases in L-type Ca 2+ current (I Ca,L ) in atrial myocytes. 13 We have also shown that wild-type NPs (BNP and CNP) can potently increase electrical conduction in the sinoatrial node and atrial myocardium.…”

Neurohumoral Control of Heart Rate

“…Voltage-clamp studies demonstrated that CNP can inhibit L-type Ca 2+ current (ICa-L) through NPR-C binding. This inhibition involves a decrease in adenylyl cyclase activity, which leads to reduced intracellular levels of cAMP (Rose et al, 2003). These results were also demonstrated in isolated myocytes from mouse SA node, that express several cAMPsensitive currents, including ICa-L (DiFrancesco, 1993).…”