Porphyrin Induced Calcium Release from Skeletal Muscle Sarcoplasmic Reticulum

Micromolar concentrations of the porphyrin mesotetra(4-N-methylpyridyl)porphine tetrajodide is shown to induce rapid release of Ca2+ from skeletal muscle sarcoplasmic reticulum vesicles. Porphyrin-induced Ca2+ release is stimulated by ATP (KdATP 100 μM) and Ca2+ (KdCa = 1 μM) and is inhibited by Mg2+ (KI = 220 pM) and rutheniuni red (KI = 7 nM). The porphyrin is also shown to stimulate high affinity [3H]ryanodine binding by decreasing the dissociation constant (kd) and increasing the binding capacity (Bmax). Moreover, in the presence of Mg2+, receptor binding is sensitized to activation by Ca2+, and porphyrin-stimulated channel activity is sensitized to activation by Ca2+. These observations show that porphyrin-induced Ca2+ release is due to a direct interaction with the Ca2+ release protein from sarcoplasmic reticulum.