Transmembrane redox sensor of ryanodine receptor complex

W. Feng, G. Liu, P. D. Allen, Isaac N Pessah

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

Inositol 1,4,5-trisphosphate receptors (IP3R) and ryanodine receptors (RyR) mediate the release of endoplasmic and sarcoplasmic reticulum (ER/SR) Ca2+ stores and regulate Ca2+ entry through voltage-dependent or ligand-gated channels of the plasma membrane. A prominent property of ER/SR Ca2+ channels is exquisite sensitivity to sulfhydryl-modifying reagents. A plausible role for sulfhydryl chemistry in physiologic regulation of Ca2+ release channels and the fidelity of Ca2+ release from ER/SR is lacking. This study reveals the existence of a transmembrane redox sensor within the RyR1 channel complex that confers tight regulation of channel activity in response to changes in transmembrane redox potential produced by cytoplasmic and luminal glutathione. A transporter selective for glutathione is co-localized with RyR1 within the SR membrane to maintain local redox potential gradients consistent with redox regulation of ER/SR Ca2+ release. Hyperreactive sulfhydryls previously shown to reside within the RyR1 complex (Liu, G., and Pessah, I. N. (1994) J. Biol. Chem. 269, 33028-33034) are an essential biochemical component of a transmembrane redox sensor. Transmembrane redox sensing may represent a fundamental mechanism by which ER/SR Ca2+ channels respond to localized changes in transmembrane glutathione redox potential produced by physiologic and pathophysiologic modulators of Ca2+ release from stores.

Original languageEnglish (US)
Pages (from-to)35902-35907
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number46
DOIs
StatePublished - Nov 17 2000

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Ryanodine Receptor Calcium Release Channel
Oxidation-Reduction
Sensors
Glutathione
Ligand-Gated Ion Channels
Inositol 1,4,5-Trisphosphate Receptors
Sulfhydryl Reagents
Sarcoplasmic Reticulum
Cell membranes
Endoplasmic Reticulum
Membrane Potentials
Modulators
Cell Membrane
Membranes
Electric potential

ASJC Scopus subject areas

  • Biochemistry

Cite this

Transmembrane redox sensor of ryanodine receptor complex. / Feng, W.; Liu, G.; Allen, P. D.; Pessah, Isaac N.

In: Journal of Biological Chemistry, Vol. 275, No. 46, 17.11.2000, p. 35902-35907.

Research output: Contribution to journalArticle

Feng, W. ; Liu, G. ; Allen, P. D. ; Pessah, Isaac N. / Transmembrane redox sensor of ryanodine receptor complex. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 46. pp. 35902-35907.
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