A, following store depletion with 1 μm thapsigargin, perfusion of 0.5 mm Mn2+ (filled bars) caused rapid quench of fura-2 emission in control myotubes (n= 56). B, Mn2+ quench was not different in myotubes transfected with negative control siRNAs (n= 23). C–E, fura-2 quench during Mn2+ addition was eliminated in myotubes transfected with either STIM1 siRNA (C, n= 13) or following expression of E106Q (D, n= 13) and markedly reduced in myotubes expressing E190Q (E, n= 10). F, summary of maximum rate of store-dependent Mn2+ quench for the conditions shown in A–E and for RyR1-null (dyspedic) myotubes (n= 13). **P < 0.01.