Key result
Treatment of E4032A-expressing cells with 200-500 µM ryanodine restores the responsiveness of the mutant channels to depolarization and RyR agonists, indicating an allosteric interaction.
Population
1B5 (RyR null/dyspedic) myotubes expressing RyR1 point mutant E4032A
Design
Preclinical
Authors
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No immediate clinical implications for RyR channelopathies; leaves open whether allosteric modulation can be harnessed therapeutically.
Ryanodine binds to sites that allosterically induce substantial conformational changes in the RyR, overcoming unfavorable energy barriers introduced by the E4032A mutation to restore channel function.
Fessenden et al. (2001) studied this question. Ryanodine vs. Untreated E4032A mutant channels was evaluated on Channel responsiveness to depolarization and RyR agonists. Treatment of E4032A-expressing cells with 200-500 µM ryanodine restores the responsiveness of the mutant channels to depolarization and RyR agonists, indicating an allosteric interaction.
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