Elevated intracellular Ca2+ and myofibrillar Ca2+ sensitivity cause iodoacetate-induced muscle contractures

Ischemic stimulation of iodoacetic acid (IAA)-treated rat extensor digitorum longus (EDL) muscles produced contractures. Similar ischemic stimulation of control EDL muscles did not result in contracture. At the onset of contracture, ATP concentration was not reduced, phosphocreatine concentration was reduced > 75%, ADP concentration was increased 9-fold, Ca2+ concentration ([Ca2+]) was increased approximately 11-fold, and inorganic phosphate concentration increased less in IAA-treated muscles than in stimulated control muscles. To test whether contracture resulted from elevated [Ca2+] and/or increased Ca2+ sensitivity of the contractile proteins, this laboratory made skinned fiber-activating solutions that simulated four different conditions: unstimulated IAA-treated and control muscles, IAA-treated muscles at contracture, and ischemically simulated control muscles. Skinned EDL fibers had lower single-fiber tensions and reduced Ca2+ sensitivities in activating solutions that mimicked the conditions in stimulated control muscles compared with activating solutions that simulated the conditions in unstimulated muscles. In contrast, the maximum tension was maintained and Ca2+ sensitivity was increased in activating solutions that simulated contracture. Tension at contracture resulted from increased intracellular [Ca2+] and increased myofibrillar Ca2+ sensitivity compared with the Ca2+ sensitivity of stimulated control fibers.