Hypochlorous acid modifies calcium release channel function from skeletal muscle sarcoplasmic reticulum

Terence G. Favero, Jason Webb, Maria Papiez, Erin Fisher, Robert J. Trippichio, Michael Broide, Jonathan J. Abramson

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

We have previously demonstrated that H2O2 at millimolar concentrations induces Ca2+ release from actively loaded sarcoplasmic reticulum (SR) vesicles and induces biphasic [3H]ryanodine binding behavior. Considering that hypochlorous acid (HOCl) is a related free radical and has been demonstrated to be a more effective oxidant of proteins, we evaluated the effects of HOCl on sarcoplasmic reticulum Ca2+-channel release mechanism. In a concentration-dependent manner, HOCl activates the SR Ca2+ release channel and induces rapid release of Ca from actively loaded vesicles. HOCl-induced Ca2+ release is inhibited in the presence of millimolar concentrations of DMSO. High-affinity [3H]ryanodine binding is also enhanced at concentrations from 10 to 100 μM. At HOCl concentrations of >100 μM, equilibrium binding is inhibited. HOCl stimulation of binding is inhibited by the addition of dithiothreitol. The direct interaction between HOCl and the Ca2+ release mechanism was further demonstrated in single-channel reconstitution experiments. HOCl, at 20 μM, activated the Ca2+ release channel after fusion of a SR vesicle to a bilayer lipid membrane. At 40 μM, Ca2+-channel activity was inhibited. Pretreatment of SR vesicles with HOCl inhibited the fluorescence development of a fluorogenic probe specific to thiol groups critical to channel function. These results suggest that HOCl at micromolar concentrations can modify SR Ca2+ handling.

Original languageEnglish (US)
Pages (from-to)1387-1394
Number of pages8
JournalJournal of Applied Physiology
Volume94
Issue number4
DOIs
StatePublished - Apr 1 2003
Externally publishedYes

Keywords

  • Reactive oxygen
  • Redox modification
  • Ryanodine binding

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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