Voltage-gated potassium channel proteins and stereoselective S-nitroso-l-cysteine signaling
| العنوان: | Voltage-gated potassium channel proteins and stereoselective S-nitroso-l-cysteine signaling |
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| المؤلفون: | Diana Kunze, Nadzeya Marozkina, Patrick Wintrobe, Tatiana S Morozkina, Tristan H. Lewis, Stephen J. Lewis, James N. Bates, James M. Seckler, Benjamin Gaston, Spencer T. Burton, Craig A. Hodges, Janna Kiselar, Jürgen Bosch, Laura Smith, Paulina M. Getsy, Timothy Strassmaier, Kellen E. McGee |
| المصدر: | JCI Insight, Vol 5, Iss 18 (2020) JCI Insight |
| بيانات النشر: | American Society for Clinical investigation, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Cell biology, Patch-Clamp Techniques, Proteome, Rats, Sprague-Dawley, Mice, 03 medical and health sciences, 0302 clinical medicine, Affinity chromatography, Animals, Cysteine, Patch clamp, Receptor, S-Nitrosothiols, Voltage-gated ion channel, Chemistry, Respiration, Stereoisomerism, General Medicine, Voltage-gated potassium channel, Ligand (biochemistry), Potassium channel, Rats, Mice, Inbred C57BL, 030104 developmental biology, Potassium Channels, Voltage-Gated, 030220 oncology & carcinogenesis, Biophysics, Medicine, Ganglia, Signal transduction, Research Article, Signal Transduction |
| الوصف: | S-nitroso-l-cysteine (L-CSNO) behaves as a ligand. Its soluble guanylate cyclase–independent (sGC-independent) effects are stereoselective — that is, not recapitulated by S-nitroso-d-cysteine (D-CSNO) — and are inhibited by chemical congeners. However, candidate L-CSNO receptors have not been identified. Here, we have used 2 complementary affinity chromatography assays — followed by unbiased proteomic analysis — to identify voltage-gated K+ channel (Kv) proteins as binding partners for L-CSNO. Stereoselective L-CSNO–Kv interaction was confirmed structurally and functionally using surface plasmon resonance spectroscopy; hydrogen deuterium exchange; and, in Kv1.1/Kv1.2/Kvβ2-overexpressing cells, patch clamp assays. Remarkably, these sGC-independent L-CSNO effects did not involve S-nitrosylation of Kv proteins. In isolated rat and mouse respiratory control (petrosyl) ganglia, L-CSNO stereoselectively inhibited Kv channel function. Genetic ablation of Kv1.1 prevented this effect. In intact animals, L-CSNO injection at the level of the carotid body dramatically and stereoselectively increased minute ventilation while having no effect on blood pressure; this effect was inhibited by the L-CSNO congener S-methyl-l-cysteine. Kv proteins are physiologically relevant targets of endogenous L-CSNO. This may be a signaling pathway of broad relevance. Two complementary affinity chromatography assays, followed by unbiased proteomic analysis, identified voltage-gated K+ channel (Kv) proteins as binding partners for S-nitroso-l-cysteine (L-CSNO). |
| اللغة: | English |
| تدمد: | 2379-3708 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1b2e357d384fc0d275b5c6b7647d2f2cTest https://doaj.org/article/0d6ea0f326f84f139e9fc944a5002b14Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1b2e357d384fc0d275b5c6b7647d2f2c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23793708 |
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