S-glutathionylation decreases Mg2+ inhibition and S-nitrosylation enhances Ca2+ activation of RyR1 channels

Aracena P.; Sánchez G; Donoso P.; Hamilton, SL; Hidalgo C.

Abstract

We have analyzed the effects of the endogenous redox-active agents S-nitrosoglutathione and glutathione disulfide, and the NO donor NOR-3, on calcium release kinetics mediated by ryanodine receptor channels. Incubation of triad-enriched sarcoplasmic reticulum vesicles isolated from mammalian skeletal muscle with these three agents elicits different responses. Glutathione disulfide significantly reduces the inhibitory effect of Mg2+ without altering Ca2+ activation of release kinetics, whereas NOR-3 enhances Ca2+ activation of release kinetics without altering Mg 2+ inhibition. Incubation with S-nitrosoglutathione produces both effects; it significantly enhances Ca2+ activation of release kinetics and diminishes the inhibitory effect of Mg2+ on this process. Triad incubation with [35S]nitrosoglutathione at pCa 5 promoted 35S incorporation into 2.5 cysteine residues per channel monomer; this incorporation decreased significantly at pCa 9. These findings indicate that S-nitrosoglutathione supports S-glutathionylation as well as the reported S-nitrosylation of ryanodine receptor channels (Sun, J., Xu, L., Eu, J. P., Stamler, J. S., and Meissner, G. (2003) J. Biol. Chem. 278, 8184-8189). The combined results suggest that S-glutathionylation of specific cysteine residues can modulate channel inhibition by Mg2+, whereas S-nitrosylation of different cysteines can modulate the activation of the channel by Ca2+. Possible physiological and pathological implications of the activation of skeletal Ca2+ release channels by endogenous redox species are discussed.

Más información

Título según WOS: S-glutathionylation decreases Mg2+ inhibition and S-nitrosylation enhances Ca2+ activation of RyR1 channels
Título según SCOPUS: S-Glutathionylation Decreases Mg2+ Inhibition and S-Nitrosylation Enhances Ca2+ Activation of RyR1 Channels
Título de la Revista: JOURNAL OF BIOLOGICAL CHEMISTRY
Volumen: 278
Número: 44
Editorial: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Fecha de publicación: 2003
Página de inicio: 42927
Página final: 42935
Idioma: English
URL: http://www.jbc.org/cgi/doi/10.1074/jbc.M306969200
DOI:

10.1074/jbc.M306969200

Notas: ISI, SCOPUS