ENHANCING EFFECT OF CALMODULIN ON CA2+-INDUCED CA2+ RELEASE IN THE SARCOPLASMIC-RETICULUM OF RABBIT SKELETAL-MUSCLE FIBERS

1. We analysed the effect of calmodulin on Ca2+-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. saponin-skinned fibres, calmodulin potentiated Ca2+ release at low Ca2+ concentrations (< 3 mu M), while it showed an inhibitory effect at high Ca2+ concentrations (3-30 mu M). 3. Co-application of ryanodine and calmodulin at 0.3 mu M 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 mu M) than for inhibition at]nigh Ca2+ concentrations (10 mu M). 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 mu M 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.