Why the study?
Hyperactivation of RyR causes skeletal muscle and arrhythmogenic heart diseases, making RyR inhibitors potential treatments, but assays are needed to evaluate channel activity for drug discovery.
Provides standardized assay protocols for identifying and evaluating ryanodine receptor inhibitors for the treatment of skeletal muscle and arrhythmogenic heart diseases.
Standardized RyR assays may accelerate preclinical inhibitor screening; leaves open clinical translation for skeletal muscle and arrhythmogenic heart diseases.
The ryanodine receptor (RyR) is a Ca 2+ release channel that is present in the sarcoplasmic reticulum and endoplasmic reticulum (ER) and that plays a central role in excitation‐contraction coupling in skeletal and cardiac muscle. Hyperactivation of RyR by genetic mutations or posttranslational modification can cause various skeletal muscle and arrhythmogenic heart diseases. Inhibitors of RyR are therefore expected to be potential drugs for treatment of such diseases. This article describes assays to evaluate RyR channel activity, including an ER Ca 2+ measurement assay that is compatible with high‐throughput screening and a [ 3 H]‐ryanodine binding assay that provides a quantitative measure of RyR channel activity as a second screen for compound hits. © 2019 by John Wiley & Sons, Inc. Basic Protocol 1 : [Ca 2+ ] ER assay for ryanodine receptor (RyR) channel activity Support Protocol 1 : Determination of dose dependence and isoform selectivity of RyR inhibitors using [Ca 2+ ] ER assay Basic Protocol 2 : [ 3 H]‐Ryanodine binding assay for RyR channel activity Support Protocol 2 : Isolation of microsomes from RyR‐expressing HEK293 cells
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Murayama et al. (2019) studied this question.
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