کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8475171 | 1550444 | 2013 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Nitric oxide regulates cardiac intracellular Na+ and Ca2 + by modulating Na/K ATPase via PKCε and phospholemman-dependent mechanism
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کلمات کلیدی
EGTAARVMN(G)-nitro-l-arginine methyl esterPLBBDMguanylate cyclaseVASPPLMbisindolylmaleimidePKC2,3-Butanedione monoxime - 2،3-Butanedione monoximel-NAME - L-NAMEArrhythmia - آریتمیethylene glycol tetraacetic acid - اتیلن گلیکول تتراستیک اسیدBIS - بهPhospholemman - فسفلومنphospholamban - فسفولامبنVentricular fibrillation - فیبریلاسیون بطنیadult rat ventricular myocytes - میوکسی های بطنی بالغ رتNitric oxide - نیتریک اکسیدProtein kinase C - پروتئین کیناز سیSodium pump - پمپ سدیم
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Nitric oxide regulates cardiac intracellular Na+ and Ca2 + by modulating Na/K ATPase via PKCε and phospholemman-dependent mechanism Nitric oxide regulates cardiac intracellular Na+ and Ca2 + by modulating Na/K ATPase via PKCε and phospholemman-dependent mechanism](/preview/png/8475171.png)
چکیده انگلیسی
In the heart, Na/K-ATPase regulates intracellular Na+ and Ca2 + (via NCX), thereby preventing Na+ and Ca2 + overload and arrhythmias. Here, we test the hypothesis that nitric oxide (NO) regulates cardiac intracellular Na+ and Ca2 + and investigate mechanisms and physiological consequences involved. Effects of both exogenous NO (via NO-donors) and endogenously synthesized NO (via field-stimulation of ventricular myocytes) were assessed in this study. Field stimulation of rat ventricular myocytes significantly increased endogenous NO (18 ± 2 μM), PKCε activation (82 ± 12%), phospholemman phosphorylation (at Ser-63 and Ser-68) and Na/K-ATPase activity (measured by DAF-FM dye, western-blotting and biochemical assay, respectively; p < 0.05, n = 6) and all were abolished by Ca2 +-chelation (EGTA 10 mM) or NOS inhibition l-NAME (1 mM). Exogenously added NO (spermine-NONO-ate) stimulated Na/K-ATPase (EC50 = 3.8 μM; n = 6/grp), via decrease in Km, in PLMWT but not PLMKO or PLM3SA myocytes (where phospholemman cannot be phosphorylated) as measured by whole-cell perforated-patch clamp. Field-stimulation with l-NAME or PKC-inhibitor (2 μM Bis) resulted in elevated intracellular Na+ (22 ± 1.5 and 24 ± 2 respectively, vs. 14 ± 0.6 mM in controls) in SBFI-AM-loaded rat myocytes. Arrhythmia incidence was significantly increased in rat hearts paced in the presence of l-NAME (and this was reversed by l-arginine), as well as in PLM3SA mouse hearts but not PLMWT and PLMKO. We provide physiological and biochemical evidence for a novel regulatory pathway whereby NO activates Na/K-ATPase via phospholemman phosphorylation and thereby limits Na+ and Ca2 + overload and arrhythmias. This article is part of a Special Issue entitled “Na+ Regulation in Cardiac Myocytes”.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 61, August 2013, Pages 164-171
Journal: Journal of Molecular and Cellular Cardiology - Volume 61, August 2013, Pages 164-171
نویسندگان
Davor Pavlovic, Andrew R. Hall, Erika J. Kennington, Karen Aughton, Andrii Boguslavskyi, William Fuller, Sanda Despa, Donald M. Bers, Michael J. Shattock,