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The Journal of General Physiology 118 3 Cover picture: Models depicting two distinct cellular mechanisms for muscle weakness in central core disease (CCD). Point mutations in the N-terminal cytoplasmic foot region of RyR1 (e.g. Y523S) result in leaky Ca²⁺ release channels by reducing a voltage-independent equilibrium constant (K) that governs ligand-modulated gating of RyR1. Alternatively, a point mutation in the COOH terminus of RyR1 (I4897T) abolishes voltage-gated SR Ca²⁺ release (EC uncoupling). See related article by Avila, G., and R.T. Dirksen in this issue, pp. 277-290.

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