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

Abstract

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(V)2.1 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.

hESC- and hiPSC-derived Schwann cells are molecularly comparable and functionally equivalent

“…The antibody array data for all proteins were also analyzed by unpaired t-test with Welch correction to account for potential unequal variance but no significant differentially expressed proteins were identified ( Table S8 ). And only a portion of most divergently expressed and nearest to statistical significance proteins have been linked to Schwann cell/myelin function: Fibronectin ( p = 0.4089), Fibrinogen ( p = 0.3715) and Integrin alpha V ( p = 0.5132) for extracellular matrix, 26 , 27 , 28 FGFR1 ( p = 0.4121) for differentiation and migration, 29 , 30 BNP ( p = 0.3772) for proliferation 31 and Progranulin ( p = 0.1625) and MIF ( p = 0.1303) for nerve regeneration 32 , 33 ( Figures 3 C and 3D).

Figure 3 Insignificant proteome differences between hESC- and hiPSC-derived Schwann cells Protein lysates were collected from passage three hESC- and hiPSC-derived Schwann cells and antibody array was performed.

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The significance of natriuretic peptide in treatment of pulmonary hypertension after mitral valve replacement

“…A number of studies have shown that thromboxane A2 (TXA2) and cyclic guanosine monophosphate (cGMP) play important roles in the regulation of pulmonary vasoconstriction. 8,9 In this study, the mechanisms of the 2 drugs in lowering PAP were compared further by detecting the concentration changes in TXA2 and cGMP before and after treatment.…”