• mostly missense mutations of the gene
  
  
• causes a point change in the amino acid sequence
  
  
• most common and frightful mutations are liked to malignant hyperthermia and central core disease
  
  
• channel is closed by interaction between the N-terminal and the central domains of the ryanodine receptor protein
  
  
• these two domains have many ligand binding sites are are located outside of the sarcoplasmic reticulum
  
  
• 22 mutations discovered in these two domains that make the channel hypersensitive to certain ligands (some found in anesthetics)
  
  
• [diagram]

Wagenknecht et al., 1997