“…Higher specific ryanodine binding, indicative of a higher channel open probability and increased sensitivity to activation by micromolar calcium and caffeine was demonstrated in MH-susceptible, p.R615C mutationpositive specimens [Ohta et al, 1989;Mickelson and Louis, 1996]. Four further methods, using tissue prepared from MH-susceptible (MHS) individuals (diagnosed by the in vitro muscle biopsy contracture test [IVCT]) or MHS individuals in which a specific mutation had been identified, have allowed the effects of specific agents on RYR1 channel function to be assessed, but do not allow independent assessment of RYR1 genotype on a controlled background and include analysis of: 1) cultured myotubes [Brinkmeier et al, 1999;Wehner et al, 2002;Wehner et al, 2004;Ducreux et al, 2004]; 2) microsomal SR fractions [Richter et al, 1997]; 3) single muscle fibers [Struk et al, 1998;Duke et al, 2002Duke et al, , 2004; and 4) lymphoblastoid cell lines [Girard et al, 2001;Tilgen et al, 2001].…”