ABSENCE OF CA2-MUSCLE OF TRANSGENIC MICE LACKING THE TYPE-1 RYANODINERECEPTOR( CURRENT FACILITATION IN SKELETAL)

1. Whole-cell patch-clamp recordings were used to study voltage-depend ent facilitation of Ca2+ currents and excessive Ca2+ tail currents in skeletal myoballs cultured from wild-type and transgenic mice expressi ng a null mutation of the ryanodine receptor (RyR) type 1 (dyspedic my oballs). 2. Ca2+ current density in dyspedic myoballs was reduced by a bout 60% compared with wild-type cells, with dihydropyridine-binding c apacity largely retained.3. Strong and long-lasting depolarizations (80 mV and 600 ms), which normally produce excessive tail currents upon repolarization in control cells, failed to do so in dyspedic myoballs . 4. Dyspedic myoballs also failed to produce both Ca2+ current facili tation and the left shift of the current-voltage (I-V) curve induced b y paired-pulse stimulation. 5. We propose that excessive tail currents and facilitation arise from silent Ca2+ channels acting as the voltag e sensors in excitation-contraction coupling.