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


Journal Article

We have previously demonstrated that H2O2 at millimolar concentrations induces Ca(2+) release from actively loaded sarcoplasmic reticulum (SR) vesicles and induces biphasic [(3)H]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 Ca(2+)-channel release mechanism. In a concentration-dependent manner, HOCl activates the SR Ca(2+) release channel and induces rapid release of Ca from actively loaded vesicles. HOCl-induced Ca(2+) release is inhibited in the presence of millimolar concentrations of DMSO. High-affinity [(3)H]ryanodine binding is also enhanced at concentrations from 10 to 100 microM. At HOCl concentrations of >100 microM, equilibrium binding is inhibited. HOCl stimulation of binding is inhibited by the addition of dithiothreitol. The direct interaction between HOCl and the Ca(2+) release mechanism was further demonstrated in single-channel reconstitution experiments. HOCl, at 20 microM, activated the Ca(2+) release channel after fusion of a SR vesicle to a bilayer lipid membrane. At 40 microM, Ca(2+)-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 Ca(2+) handling.

Full Text

Duke Authors

Cited Authors

  • Favero, TG; Webb, J; Papiez, M; Fisher, E; Trippichio, RJ; Broide, M; Abramson, JJ

Published Date

  • April 2003

Published In

Volume / Issue

  • 94 / 4

Start / End Page

  • 1387 - 1394

PubMed ID

  • 12626470

Pubmed Central ID

  • 12626470

International Standard Serial Number (ISSN)

  • 8750-7587

Digital Object Identifier (DOI)

  • 10.1152/japplphysiol.00645.2002


  • eng

Conference Location

  • United States