Key result
Mutations in the S6 cytoplasmic region of RyR2 altered basal channel activity and sensitivity to activation, suggesting its interaction with the U motif stabilizes the closed state of the channel.
Population
Mouse cardiac ryanodine receptor (RyR2) and HEK293 cells
Comparison
Structure-guided site-directed mutagenesis of… vs Wild-type RyR2
Design
Preclinical
Authors
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No immediate clinical implications for arrhythmia therapy; leaves open whether S6-U motif modulation prevents spontaneous Ca2+ release in humans.
Interactions between the cytoplasmic region of S6 and the U motif of RyR2 are critical for stabilizing the closed state of the channel, with mutations in this interface increasing the propensity for spontaneous Ca2+ release and arrhythmias.
Sun et al. (2016) studied this question. Site-directed mutagenesis of the S6 cytoplasmic region of mouse RyR2 vs. Wild-type RyR2 was evaluated on Channel gating function (basal channel activity and sensitivity to activation). Mutations in the S6 cytoplasmic region of RyR2 altered basal channel activity and sensitivity to activation, suggesting its interaction with the U motif stabilizes the closed state of the channel.
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