Key result
Substitution of Gly-4941 with Lys in the RyR1 channel significantly increased the single-channel open probability to 0.89 compared to 0.13 for wildtype at 2 µM cytosolic Ca2+.
Population
HEK293 cells expressing RyR1 variants and purified RyR1 channels
Comparison
Substitution of Gly-4941 with Asp or Lys and… vs Wildtype RyR1
Design
Preclinical
Authors
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RyR1-G4941K effects in animals should not yet alter clinical practice; leaves open its role in human channelopathies.
Absolute Event Rate: 0.89% vs 0.13%
p-value: p=<0.05
The G4941K substitution in the RyR1 S6 helix alters channel gating and increases sensitivity to cytosolic and luminal Ca2+, likely through the formation of a salt bridge.
Xu et al. (2017) studied this question. G4941K substitution in RyR1 vs. Wildtype RyR1 was evaluated on Single-channel open probability (Po) at 2 µM cytosolic Ca2+ (p=<0.05). Substitution of Gly-4941 with Lys in the RyR1 channel significantly increased the single-channel open probability to 0.89 compared to 0.13 for wildtype at 2 µM cytosolic Ca2+.
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