C-type Natriuretic Peptide Inhibits L-type Ca²⁺Current in Rat Magnocellular Neurosecretory Cells by Activating the NPR-C Receptor

Abstract

(MNCs), of the paraventricular and supraoptic nuclei of the hypothalamus, secrete the hormones vasopressin and oxytocin. As a result, they have an essential role in fundamental physiological responses including regulation of blood volume and fluid homeostasis. C-type natriuretic peptide (CNP) is present at high levels in the hypothalamus. Although CNP is known to decrease hormone secretion from MNCs, no studies have examined the role of the natriuretic peptide C receptor (NPR-C) in these neurons. In this study, whole cell recordings from acutely isolated MNCs, and MNCs in a coronal slice preparation, show that CNP (2 ϫ 10 Ϫ8 M) and the selective NPR-C agonist, cANF (2 ϫ 10 Ϫ8 M), significantly inhibit L-type Ca 2ϩ current (I Ca(L) ) by ϳ50%. This effect on I Ca(L) is mimicked by dialyzing a G i -activator peptide (10 Ϫ7 M) into these cells, implicating a role for the inhibitory G protein, G i . These NPR-C-mediated effects were specific to I Ca(L) . T-type Ca 2ϩ channels were unaffected by CNP. Current-clamp experiments revealed the ability of CNP, acting via the NPR-C receptor, to decrease (ϳ25%) the number of action potentials elicited during a 500 ms depolarizing stimulus. Analysis of action potential duration revealed that CNP and cANF significantly decreased 50% repolarization time (APD 50 ) in MNCs. In summary, our findings show that CNP has a potent and selective inhibitory effect on I Ca(L) and on excitability in MNCs that is mediated by the NPR-C receptor. These data represent the first electrophysiological evidence of a functional role for the NPR-C receptor in the mammalian hypothalamus.

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).…”

C-type natriuretic peptide in individuals with normal left ventricular systolic function

“…NPR-C is initially thought to act as a clearance receptor and lacks the guanylate cyclase domain (12). However, a recent study demonstrated the electrophysiological evidence of a functional role for the NPR-C in the mammalian hypothalamus (13). There are two mechanisms by which CNP is catabolized.…”

Natriuretic peptide C receptor signalling in the heart and vasculature

“…2003, 2004) and central nervous system (Trachte et al . 1995, 2003; Rose et al . 2005) as well as muscular contraction in the gastrointestinal system (Murthy et al .…”