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Redox-sensitive stimulation of type-1 ryanodine receptors by the scorpion toxin maurocalcine.: Redox-sensitive RyR stimulation by Maurocalcine

Abstract : The scorpion toxin maurocalcine acts as a high affinity agonist of the type-1 ryanodine receptor expressed in skeletal muscle. Here, we investigated the effects of the reducing agent dithiothreitol or the oxidizing reagent thimerosal on type-1 ryanodine receptor stimulation by maurocalcine. Maurocalcine addition to sarcoplasmic reticulum vesicles actively loaded with calcium elicited Ca(2+) release from native vesicles and from vesicles pre-incubated with dithiothreitol; thimerosal addition to native vesicles after Ca(2+) uptake completion prevented this response. Maurocalcine enhanced equilibrium [(3)H]-ryanodine binding to native and to dithiothreitol-treated reticulum vesicles, and increased 5-fold the apparent Ki for Mg(2+) inhibition of [(3)H]-ryanodine binding to native vesicles. Single calcium release channels incorporated in planar lipid bilayers displayed a long-lived open sub-conductance state after maurocalcine addition. The fractional time spent in this sub-conductance state decreased when lowering cytoplasmic [Ca(2+)] from 10μM to 0.1μM or at cytoplasmic [Mg(2+)]≥30μM. At 0.1μM [Ca(2+)], only channels that displayed poor activation by Ca(2+) were readily activated by 5nM maurocalcine; subsequent incubation with thimerosal abolished the sub-conductance state induced by maurocalcine. We interpret these results as an indication that maurocalcine acts as a more effective type-1 ryanodine receptor channel agonist under reducing conditions.
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Submitted on : Thursday, July 11, 2013 - 10:58:53 AM
Last modification on : Monday, May 11, 2020 - 4:20:50 PM
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Michel Ronjat, José Pablo Finkelstein, Paola Llanos, Luis Montecinos, Hicham Bichraoui, et al.. Redox-sensitive stimulation of type-1 ryanodine receptors by the scorpion toxin maurocalcine.: Redox-sensitive RyR stimulation by Maurocalcine. Cell Calcium, Elsevier, 2013, 53 (5-6), pp.357-65. ⟨10.1016/j.ceca.2013.03.004⟩. ⟨inserm-00843353⟩

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