Monogene Ionenkanalerkrankungen der Skelettmuskulatur

Muscular channelopathies such as myotonias, dyskalemic periodic paralyses (PP), malignant hyperthermia (MH), and core myopathies are caused by mutations of Na⁺, K⁺, Ca^2+, and Cl^? channels. Mild depolarization leads to myotonic activity. Augmented membrane depolarization can convert hyperexcitability into hypoexcitability and cause transient muscle weakness. Sustained depolarization of the plasmalemma and the t-tubular membrane is the common basis of the muscle weakness in the dominant dyskalemic PP. Serum potassium levels modulate the resting membrane potential, whereby deviations from the physiological range, e.g., by thyroid dysfunction, exacerbate membrane depolarization, and weakness. Susceptibility to MH, a potentially life-threatening hypermetabolic event, is mediated by dominant mutations which are situated in the cytoplasmic part of the Ca²⁺ release channel of the sarcoplasmic reticulum and increase the sensitivity to volatile anesthetics. Dominant or recessive mutations located in the sarcoplasmic part of the channel deplete the Ca²⁺ stores and lead to weakness and finally to a core myopathy.