Enhancing effect of calmodulin on Ca(2+)-induced Ca2+ release in the sarcoplasmic reticulum of rabbit skeletal muscle fibres.
1. We analysed the effect of calmodulin on Ca(2+)-induced Ca2+ release (CICR) in the sarcoplasmic reticulum (SR) using chemically skinned fibres of rabbit psoas muscle. Ca2+ release was measured using fura-2 microfluorometry. 2. In saponin-skinned fibres, calmodulin potentiated Ca2+ release at low Ca2+ concentrations (< 3 microM), while it showed an inhibitory effect at high Ca2+ concentrations (3-30 microM). 3. Co-application of ryanodine and calmodulin at 0.3 microM Ca2+, but not ryanodine alone, induced a decline in the Ca2+ uptake capacity of the SR, an effect expected from the open-lock of active CICR channels by ryanodine. Thus, potentiation of Ca2+ release by calmodulin at low Ca2+ concentrations can be regarded as a result of the activation of the ryanodine receptor. 4. Greater concentrations of calmodulin were required for potentiation of CICR at low Ca2+ concentrations (1 microM) than for inhibition at high Ca2+ concentrations (10 microM). 5. In beta-escin-permeabilized fibres in which intrinsic calmodulin was retained, the rates of CICR were similar to those measured in the presence of 1 microM calmodulin in saponin-permeabilized fibres. 6. These results suggest that calmodulin plays an important role in the regulation of CICR channels in intact skeletal muscle fibres.
Department of Pharmacology, Faculty of Medicine, University of Tokyo, Japan.
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Ikemoto
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Iino
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D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002147:Calmodulin / Q000494:pharmacology*; D003592:Cytophotometry; D066298:In Vitro Techniques; D008274:Magnesium / Q000502:physiology; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009124:Muscle Proteins / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D016658:Psoas Muscles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel; D012503:Saponins / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*
D015220:Calcium Channels; D002147:Calmodulin; D009124:Muscle Proteins; D010726:Phosphodiesterase Inhibitors; D019837:Ryanodine Receptor Calcium Release Channel; D012503:Saponins; D002110:Caffeine; D008274:Magnesium; D002118:Calcium