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 language | English (US) |
|---|---|
| Pages (from-to) | 35902-35907 |
| Number of pages | 6 |
| Journal | Journal of Biological Chemistry |
| Volume | 275 |
| Issue number | 46 |
| DOIs | |
| State | Published - Nov 17 2000 |
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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 journal › Article
}
TY - JOUR
T1 - Transmembrane redox sensor of ryanodine receptor complex
AU - Feng, W.
AU - Liu, G.
AU - Allen, P. D.
AU - Pessah, Isaac N
PY - 2000/11/17
Y1 - 2000/11/17
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0034680790&partnerID=8YFLogxK
U2 - 10.1074/jbc.C000523200
DO - 10.1074/jbc.C000523200
M3 - Article
C2 - 10998414
AN - SCOPUS:0034680790
VL - 275
SP - 35902
EP - 35907
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 46
ER -