Fig. 1: Inhibition of RyR1 by Mg²⁺.

a Ryanodine binding to rabbit skeletal SR membrane vesicles demonstrates a biphasic response of RyR1 over a wide range of Ca²⁺ concentrations (100 nM–2 mM). At all Ca²⁺ concentrations, ATP (2 mM) increased ryanodine binding, whereas Mg²⁺ alone (1 mM) or Mg²⁺/ATP (5 mM each) abolished channel activity. b Progressive inhibition of RyR1 by Mg²⁺ (from 1 μM to 5 mM) in the presence or absence of equivalent concentrations of ATP, and progressive activation of RyR1 by ATP (from 1 μM to 5 mM). Ca²⁺ concentration was 50 μM for all data points. c At 50 μM Ca²⁺, Mg²⁺/ATP (5 mM each) abrogated RyR1 opening completely, while substitution of ATP by AMP-PCP resulted in further activation of the channel and incomplete inhibition by Mg²⁺, respectively. Data represent mean±SEM specific [³H] ryanodine binding from three independent experiments. pCa = −log₁₀ [Ca²⁺], pMg = −log₁₀ [Mg²⁺], pATP = −log₁₀ [ATP].