Activation of atrial natriuretic peptide receptor A depresses hypothalamic PVN CRFergic neuronal excitability by inhibiting IH in vitro in mice

Atrial natriuretic peptide (ANP) and its receptor are abundantly distributed in hypothalamic paraventricular nucleus (PVN), and contribute to regulation of corticotropin releasing factor (CRF) release in the brain. However, the mechanism by which ANP regulates the activity of PVN CRFergic neurons remains unclear. Here, we investigated the mechanism by which ANP modulates the neuronal activity related to PVN CRF-mRNA expression in vitro in mice using whole-cell patch-clamp recording, single-cell RT-PCR, immunofluorescence, and pharmacological methods. Our data demonstrated that ANP significantly reduced the membrane excitability of PVN neurons expressing CRF-mRNA. This effect was abolished by an antagonist of ANP receptor A (NPR − A), namely A71915. Furthermore, ANP significantly suppressed the hyperpolarization − activated cationic currents (I_h) of neurons expressing CRF-mRNA. Blockade of either I_h or NPR − A completely prevented this inhibitory effect. Immunohistochemistry results indicated that NPR − A immunoreactivity was present in PVN CRF-positive neurons. These findings suggest that ANP decreases the excitability of PVN CRFergic neurons via NPR − A − mediated inhibition of I_h channel activity in vitro in mice.