Brain natriuretic peptide modulates the delayed rectifier outward K+ current and promotes the proliferation of mouse schwann cells

Brain natriuretic peptide (BNP) may act as a neuromodulator via its associated receptors (natriuretic peptide receptors, NPRs) in the central nervous system (CNS), but few studies have reported its activity in the peripheral nervous system (PNS). In this study, we observed that BNP increased the tetraethylammonium chloride (TEA)‐sensitive delayed rectifier outward potassium current (I_K) in mouse Schwann cells (SCs) using whole‐cell recording techniques. At concentrations of 1–100 nM, BNP reversibly activated I_K in a dose‐dependent manner, with modulating its steady‐state activation and inactivation properties. The effect of BNP on I_K was abolished by preincubation with the specific antagonist of NPR‐A, and could not be mimicked by application of NPR‐C agonist. These results were supported by immunocytochemical findings indicating that NPR‐A was expressed in SCs. The application of 8‐Br‐guanosine 3′,5′‐monophosphate (8‐Br‐cGMP) mimicked the effect of BNP on I_K, but BNP was unable to further increase I_K after the application of cyclic guanosine monophosphate (cGMP). Genistein blocked I_K and also completely eliminated the effects of BNP and cGMP on I_K. The selective K_V2.1 subunit blocker, Jingzhaotoxin‐III (JZTX‐III), reduced I_K amplitude by 30%, but did not abolish the increase effect of BNP on I_K amplitude. In addition, BNP significantly stimulated SCs proliferation and this effect could be partly inhibited by TEA. Together these results suggest that BNP modulated I_K probably via cGMP‐ and tyrosine kinase‐dependent pathways by activation of NPR‐A. This effect of BNP on I_K in SCs might partly explain its effect on cell proliferation. J. Cell. Physiol. 226: 440–449, 2011. © 2010 Wiley‐Liss, Inc.