Table 2.
Activation of wild-type and mutant RyRs by Ca2+
| EC50, μM |
||||
|---|---|---|---|---|
| Mutation | Myopathy | No Mg2+ | 1 mM Mg2+ | |
| WT-RyR1 | 1.0 ± 0.1 (5) | 2.0 ± 0.1 (4) | ||
| EF-hand | T4082M | MH | 0.74 ± 0.08 (5) | ND |
| S4113L | CNM | 1.2 ± 0.1 (5) | ND | |
| N4120Y | MH | 0.91 ± 0.11 (5) | ND | |
| S2–S3 loop | F4732D | MH | 0.66 ± 0.13 (4) | 1.4 ± 0.2 (7) |
| G4733E | MH | 0.73 ± 0.05 (4) | 1.4 ± 0.2 (5) | |
| R4736W | MH | 0.96 ± 0.09 (7) | 1.4 ± 0.1 (5) | |
| R4736Q | MH | 1.2 ± 0.1 (5) | 1.4 ± 0.2 (6) | |
| S4–S5 loop | T4825I | MH | 0.22 ± 0.02*(6) | 0.94 ± 0.05* (4) |
| H4832Y | MH | 0.41 ± 0.09*(5) | 0.51 ± 0.03* (4) | |
| WT-RyR2 | 4.2 ± 2.5 (5) | 1.9 ± 0.04 (8) | ||
Values are means ± SE of the number of experiments indicated in parentheses. EC50 values for Ca2+-dependent activation of wild-type and mutant RyRs were determined in the absence and presence of 1 mM Mg2+. RyR1 mutations are associated with either malignant hyperthermia (MH) or centronuclear myopathy (CNM).
*
P < 0.05 compared with WT-RyR1 by one-way ANOVA followed by Tukey's test among RyR1 groups (wild-type and mutant RyR1s). ND, not determined.