Calcium-Induced Calcium Release Test
We have previously demonstrated  that, in skeletal muscle biopsied from a patient with typical malignant hyperthermia (MH) syndrome, Ca-induced Ca release (CICR) in the sarcoplasmic reticulum (SR) was accelerated, while the Ca pump activity of the SR and the Ca sensitivity of the contractile system in the muscle were normal. Therefore, it appeared important to further examine the rate of CICR in muscles from patients in whom MH was suspected. We examined biopsied muscles from 84 subjects, 79 in whom MH was suspected and 5 normal (non-MH-suspected) controls. Skinned fibers were prepared from each specimen and the rates of Ca release were measured at 0, 0.3, 1.0, 3.0, and 10 μM Ca. Since the number of normal control specimens was too small to establish the range of the normal rate of CICR, cluster analysis based on the Ca release rates was made on all the data obtained. As already reported , the subjects examined were objectively classified into three groups according to the rate of CICR: unaccelerated (group 1, n = 61), moderately accelerated (group 2, n = 19), and highly accelerated (group 3, n = 4). The normal controls were all in group 1. Almost all the patients with conspicuous fever (≥40.0°C and/or ≥0.5°C rise/15 min) during anesthesia belonged to group two or three. These results suggest that, in the majority of MH patients, the abnormality in the CICR in skeletal muscle SR is involved in the cause of the disease. There could be other causes of the MH syndrome, and for this reason in particular, the CICR test should be fully utilized when genetic studies of the ryanodine receptor are conducted.
KeywordsSkeletal Muscle Sarcoplasmic Reticulum Ryanodine Receptor Malignant Hyperthermia Malignant Hyperthermia
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