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(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.
Fei
Xiao-Wei
XW
Institutes of Brain Science, School of Life Sciences and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
Pan
Chen-Jie
CJ
He
Yan-Lin
YL
Fang
Yan-Jia
YJ
Zhuang
Jia-Li
JL
Mei
Yan-Ai
YA
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D000242:Cyclic AMP / Q000737:chemistry / Q000378:metabolism; D051668:Delayed Rectifier Potassium Channels / Q000378:metabolism*; D019833:Genistein / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D013111:Spider Venoms / Q000378:metabolism; D019789:Tetraethylammonium / Q000378:metabolism
D051668:Delayed Rectifier Potassium Channels; D010455:Peptides; D047428:Protein Kinase Inhibitors; D021122:Protein Subunits; D013111:Spider Venoms; C487820:jingzhaotoxin-III, Chilobrachys jingzhao; D020097:Natriuretic Peptide, Brain; D019789:Tetraethylammonium; D019833:Genistein; D000242:Cyclic AMP