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

2003 ◽  
Vol 94 (4) ◽  
pp. 1387-1394 ◽  
Author(s):  
Terence G. Favero ◽  
Jason Webb ◽  
Maria Papiez ◽  
Erin Fisher ◽  
Robert J. Trippichio ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Calcium Release ◽  
Lipid Membrane ◽  
Hypochlorous Acid ◽  
Release Mechanism ◽  
Dependent Manner ◽  
Calcium Release Channel ◽  
Release Channel ◽  
Binding Behavior ◽  
Channel Function

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.

scholarly journals Sphingosylphosphocholine modulates the ryanodine receptor/calcium-release channel of cardiac sarcoplasmic reticulum membranes

1997 ◽  
Vol 322 (1) ◽  
pp. 327-333 ◽  
Author(s):  
Romeo BETTO ◽  
Alessandra TERESI ◽  
Federica TURCATO ◽  
Giovanni SALVIATI ◽  
Roger A. SABBADINI ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Ryanodine Receptor ◽  
Calcium Release ◽  
Cardiac Tissue ◽  
Ruthenium Red ◽  
Release Mechanism ◽  
Calcium Release Channel ◽  
Release Channel ◽  
Cardiac Sarcoplasmic Reticulum ◽  
High Calcium

Sphingosylphosphocholine (SPC) modulates Ca2+ release from isolated cardiac sarcoplasmic reticulum membranes; 50 ƁM SPC induces the release of 70Ő80% of the accumulated calcium. SPC releases calcium from cardiac sarcoplasmic reticulum through the ryanodine receptor, since the release is inhibited by the ryanodine receptor channel antagonists ryanodine, Ruthenium Red and sphingosine. In intact cardiac myocytes, even in the absence of extracellular calcium, SPC causes a rise in diastolic Ca2+, which is greatly reduced when the sarcoplasmic reticulum is depleted of Ca2+ by prior thapsigargin treatment. SPC action on the ryanodine receptor is Ca2+-dependent. SPC shifts to the left the Ca2+-dependence of [3H]ryanodine binding, but only at high pCa values, suggesting that SPC might increase the sensitivity to calcium of the Ca2+-induced Ca2+-release mechanism. At high calcium concentrations (pCa 4.0 or lower), where [3H]ryanodine binding is maximally stimulated, no effect of SPC is observed. We conclude that SPC releases calcium from cardiac sarcoplasmic reticulum membranes by activating the ryanodine receptor and possibly another intracellular Ca2+-release channel, the sphingolipid Ca2+-release-mediating protein of endoplasmic reticulum (SCaMPER) [Mao, Kim, Almenoff, Rudner, Kearney and Kindman (1996) Proc. Natl. Acad. Sci. U.S.A 93, 1993Ő1996], which we have identified for the first time in cardiac tissue.

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