How Many Cysteine Residues Regulate Ryanodine Receptor Channel Activity?
- 1 March 2000
- journal article
- review article
- Published by Mary Ann Liebert Inc in Antioxidants and Redox Signaling
- Vol. 2 (1) , 27-34
- https://doi.org/10.1089/ars.2000.2.1-27
Abstract
RyRs contain 80–100 cysteine residues per subunit, of which ~25% are free for covalent modification, while the remainder are either modified or form intraprotein disulfides. Oxidizing and nitrosylating reagents have several effects on single RyR channel activity, which depend on the type of modifying reagent, the isoform of the RyR, and ligands bound to the channel. We present evidence here for four major classes of functional cysteine residues associated with RyR channels, i.e., two classes with free -SH groups that either activate or inhibit channels when covalently modified and two classes, with endogenous modification, that either inhibit or activate. Single-channel characteristics provide evidence for four discrete responses within the first activating class, two responses within the second inhibiting class and two types of response within the third endogenously modified class. All but one of these changes in channel properties depend on residues located on the cytoplasmic or membrane-associated domains of the RyR; the remaining response is confined to the luminal domain. If it is assumed that each type of response depends on a separate subclass of cysteine residue and that each subclass contains a minimum of one cysteine per subunit, our results suggest that there are at least nine cysteine residues per subunit with functional connections to the gating mechanism of RyR channels. These cysteine residues may be selectively modified under physiological and pathological conditions to regulate Ca2+ release from the sarcoplasmic reticulum and contraction.Keywords
This publication has 29 references indexed in Scilit:
- Determination of Time-Dependent Inositol-1,4,5-Trisphosphate Concentrations during Calcium Release in a Smooth Muscle CellBiophysical Journal, 1999
- In vitro simultaneous measurements of relaxation and nitric oxide concentration in rat superior mesenteric arteryThe Journal of Physiology, 1999
- Inactivation of Ca2+ Release Channels (Ryanodine Receptors RyR1 and RyR2) with Rapid Steps in [Ca2+] and VoltageBiophysical Journal, 1998
- Sulfhydryl Oxidation Modifies the Calcium Dependence of Ryanodine-Sensitive Calcium Channels of Excitable CellsBiophysical Journal, 1998
- Role of nitric oxide in skeletal muscle: synthesis, distribution and functional importanceActa Physiologica Scandinavica, 1998
- Glutathione Modulates Ryanodine Receptor from Skeletal Muscle Sarcoplasmic ReticulumPublished by Elsevier ,1997
- A novel phasic contraction induced by dithiothreitol in frog skeletal muscleGeneral Pharmacology: The Vascular System, 1996
- Ion channels in the sarcoplasmic reticulum of striated muscleActa Physiologica Scandinavica, 1996
- Preparation and morphology of sarcoplasmic reticulum terminal cisternae from rabbit skeletal muscle.The Journal of cell biology, 1984
- Rates of thiol-disulfide interchange reactions involving proteins and kinetic measurements of thiol pKa valuesBiochemistry, 1980