Open AccessSH Oxidation Stimulates Calcium Release Channels (Ryanodine Receptors) From Excitable Cells
Author(s) -
Cecilia Hidalgo,
Ricardo Bull,
Juan José Marengo,
Claudio F. Pérez,
P Donoso
Publication year - 2000
Publication title -
biological research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.127
H-Index - 55
eISSN - 0717-6287
pISSN - 0716-9760
DOI - 10.4067/s0716-97602000000200011
Subject(s) - ryanodine receptor , calcium , chemistry , biophysics , voltage dependent calcium channel , calsequestrin , biochemistry , t type calcium channel , ryanodine receptor 2 , vesicle , endoplasmic reticulum , calcium channel , biology , membrane , organic chemistry
The effects of redox reagents on the activity of the intracellular calcium release channels (ryanodine receptors) of skeletal and cardiac muscle, or brain cortex neurons, was examined. In lipid bilayer experiments, oxidizing agents (2,2'-dithiodipyridine or thimerosal) modified the calcium dependence of all single channels studied. After controlled oxidation channels became active at sub microM calcium concentrations and were not inhibited by increasing the calcium concentration to 0.5 mM. Subsequent reduction reversed these effects. Channels purified from amphibian skeletal muscle exhibited the same behavior, indicating that the SH groups responsible for modifying the calcium dependence belong to the channel protein. Parallel experiments that measured calcium release through these channels in sarcoplasmic reticulum vesicles showed that following oxidation, the channels were no longer inhibited by sub mM concentrations of Mg2+. It is proposed that channel redox state controls the high affinity sites responsible for calcium activation as well as the low affinity sites involved in Mg2+ inhibition of channel activity. The possible physiological and pathological implications of these results are discussed.