Major surgery is a nerve-racking experience under the best of conditions – but it’s even more so for patients at risk of malignant hyperthermia (MH), a genetic disorder in which anesthetics can cause the muscles to go rigid and produce excessive heat – sometimes even leading to the patient’s death. Although rare, MH is challenging to diagnose because genetic tests are reliable in only about half of cases; in the other half, painful and invasive muscle biopsies are the only way to be sure. The need for a more informative, less invasive test is clear.
My lab is interested in calcium regulation and excitation-contraction coupling in skeletal muscle, which is why studying how the ryanodine receptor (RyR) regulates this process is of high interest to us. To study these aspects of skeletal muscle physiology, we use single muscle fibers, which we mechanically “skin” by peeling away the outer plasma membrane with fine forceps to access the cytoplasmic components. In the last few years, we have moved our approaches – developed in rodent muscle – to human muscle obtained from needle biopsies. After we refined our approaches, we realized we could detect the activity of the RyR in resting muscle. These calcium movements are tiny compared with those in contracting muscle. Armed with this knowledge, we began to seek subjects with MH susceptibility. We expected to be able to observe differences in calcium handling compared with control subjects (1).
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