To investigate the effect of inositol 1,4,5-trisphosphate on calcium release, we used fiber bundles of frog sartorius muscle mechanically permeabilized by a scratching procedure, and we detected increments in calcium concentration by measuring aqueorin light signals. Submicromolar concentrations ofinositol 1,4,5-trisphosphate induced fast calcium-release signals, with a half time to peak of 60 ms or less. Similar responses were elicited by caffeine. The calcium-release signal induced by inositol 1,4,5-trisphosphate occurred at pCa values of 7 or lower, and the dose-response curve depended on the ionic composition of the incubation solution. Lower inositol 1,4,5-trisphosphate concentrations were needed to induce release when incubation solutions of ionic composition expected to depolarize the transverse tubule membrane were used. Inositol 1,4,5-trisphosphate was more effective than inositol 1,3,4-trisphosphate, inositol 1,4,5,6-tetrakisphosphate, and inositol 1,4-bisphosphate.
The effect of inositol 1,4,5-trisphosphate was synergistic with that of caffeine, and was not inhibited by heparin. These results, by showing directly that at resting calcium levels inositol 1,4,5-trisphosphate elicited calcium release, are consistent with a role for inositol 1,4,5-trisphosphate as a chemical modulator in excitation/contraction coupling in skeletal muscle.