Inositol trisphosphate stimulates calcium release from peeled skeletal muscle fibers

The effects of inositol phosphates (tris (InsP₃), bis (InsP₂), mono (InsP)) on rabbit adductor magnus and soleus muscles were determined using mechanically peeled fibers (sarcolemma removed). Isometric force generation of each fiber was continuously monitored and was used along with ⁴⁵Ca to detect calcium release from internal fiber stores. All experiments were conducted at a physiological Mg²⁺ concentration (10^-3 M) of the bathing solutions. The inositol phosphates did not directly activate the contractile apparatus. At bath concentrations of 100-300 μM, only InsP₃ was capable of stimulating Ca²⁺ release. In contrast, 1 μM InsP₃ maximally and selectively stimulated Ca²⁺ release when microinjected into the myofilament lattice. Calcium releasing effects of InsP₂ and InsP were manifested at 10 μM when they were microinjected. The end-to-end internal Ca²⁺ release and subsequent fiber force generation stimulated by the locally applied microinjected InsP₃ suggests that the InsP₃-induced Ca²⁺ release mechanism may involve propagation, but not via the Ca²⁺-induced Ca²⁺ release, since procaine did not inhibit this response. These findings support the possibility that InsP₃ plays a role in skeletal muscle excitation-contraction coupling.