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Atrial glutathione content, calcium current, and contractility

Item Type:Article
Title:Atrial glutathione content, calcium current, and contractility
Creators Name:Carnes, C.A. and Janssen, P.M.L. and Ruehr, M.L. and Nakayama, H. and Nakayama, T. and Haase, H. and Bauer, J.A. and Chung, M.K. and Fearon, I.M. and Gillinov, A.M. and Hamlin, R.L. and van Wagoner, D.R.
Abstract:Atrial fibrillation (AF) is characterized by decreased L-type calcium current (ICa,L) in atrial myocytes and decreased atrial contractility. Oxidant stress and redox modulation of calcium channels are implicated in these pathologic changes. We evaluated the relationship between glutathione content (the primary cellular reducing moiety), and ICa,L in atrial specimens from AF patients undergoing cardiac surgery. Left atrial glutathione content was significantly lower in patients with either paroxysmal or persistent AF relative to control patients with no history of AF. Incubation of atrial myocytes from AF patients (but not controls) with the glutathione precursor N-acetylcysteine caused a marked increase in ICa,L. To test the hypothesis that glutathione levels were mechanistically linked with the reduction in ICa,L, dogs were treated for 48 hours with buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis. BSO treatment resulted in a 24% reduction in canine atrial glutathione content, a reduction in atrial contractility, and an attenuation of ICa,L in the canine atrial myocytes. Incubation of these myocytes with exogenous glutathione also restored ICa,L to normal or greater than normal levels. To probe the mechanism linking decreased glutathione levels to down-regulation of ICa, the biotin switch technique was used to evaluate S-nitrosylation of calcium channels. S-nitrosylation was apparent in left atrial tissues from AF patients; extent of S-nitrosylation was inversely related to tissue glutathione content. S-nitrosylation was also detectable in HEK cells expressing recombinant human cardiac calcium channel subunits following exposure to nitrosoglutathione. S-nitrosylation may contribute to the glutathione-sensitive attenuation of ICa,L observed in AF.
Keywords:Buthionine Sulfoximine, Calcium, Cultured Cells, Glutathione, Heart Atria, Kidney, Muscle Cells, Muscle Contraction, Myocardial Contraction, Nitrogen, Patch-Clamp Techniques, Time Factors, Animals, Dogs
Source:Journal of Biological Chemistry
Publisher:American Society for Biochemistry and Molecular Biology
Page Range:28063-28073
Date:21 September 2007
Official Publication:https://doi.org/10.1074/jbc.M704893200
PubMed:View item in PubMed

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