Absence of Ca2+ current facilitation in skeletal muscle of transgenic mice lacking the type 1 ryanodine receptor.
1. Whole-cell patch-clamp recordings were used to study voltage-dependent facilitation of Ca2+ currents and excessive Ca2+ tail current in skeletal myoballs cultured from wild-type and transgenic mice expressing a null mutation of the ryanodine receptor (RyR) type 1 (dyspedic myoballs). 2. Ca2+ current density in dyspedic myoballs was reduced by about 60% compared with wild-type cells, with dihydropyridine-binding capacity 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 facilitation and the left shift of the current-voltage (I-V) curve induced by paired-pulse stimulation. 5. We propose that excessive tail currents and facilitation arise from silent Ca2+ channels acting as the voltage sensors in excitation-contraction coupling.
Max Planck Institute for Biophysical Chemistry, Göttingen, Germany. afleig@gwdg.de
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Fleig
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Takeshima
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Penner
D000818:Animals; D000831:Animals, Newborn; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004594:Electrophysiology; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009154:Mutation; D018408:Patch-Clamp Techniques; D019837:Ryanodine Receptor Calcium Release Channel
D015220:Calcium Channels; D002148:Calmodulin-Binding Proteins; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel