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Ryanodine Receptor Channel-Dependent Glutathione Transport in the Sarcoplasmic Reticulum of Skeletal Muscle

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Abstract

We found that glutathione transport across endo/sarcoplasmic reticulum membranes correlates with the abundance of ryanodine receptor type 1 (RyR1). The transport was the fastest in muscle terminal cisternae, fast in muscle microsomes and slow in liver, heart, and brain microsomes. Glutathione influx could be inhibited by RyR1 blockers and the inhibitory effect was counteracted by RyR1 agonists. The effect of blockers was specific to glutathione, as the transport of other small molecules was not hindered. Therefore, the glutathione transport activity seems to be associated with RyR1 in sarcoplasmic reticulum.

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    Abbreviations used: RyR, ryanodine receptor; ER, endoplasmic reticulum; SR, sarcoplasmic reticulum; GSH, reduced glutathione; GSSG, glutathione disulfide; Mops, 4-morpholinepropanesulfonic acid.

    1

    To whom correspondence should be addressed at Dipartimento di Fisiopatologia e Medicina Sperimentale, Viale A. Moro n°1, 53100 Siena, Italy. Fax: +0577 234009. E-mail: [email protected].

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