Muscle Channelopathies

The myotonias and familial periodic paralyses are hereditary muscle channelopathies with onset at birth or second decade, at the latest. Both have impaired muscle excitation caused by mutations in voltage-gated Na+, K+, Ca2+, and Cl− channels. Membrane hyperexcitability usually results in myotonic stiffness. Severe myotonia may cause laryngospasm resulting in cyanosis and loss of consciousness, misinterpreted as epileptic seizure. With increasing membrane depolarization, hyperexcitability can be transiently turned into hypoexcitability causing flaccid weakness. Hypoexcitability due to long-lasting depolarization that inhibits action potential generation is the common mechanism for the periodic paralyses. Episodes of weakness can be confused with episodic ataxia. Interictally, the ion channel malfunction may be compensated so that specific exogenous or endogenous provocative factors are required to produce symptoms in the patients. An especially obvious and therefore name-giving triggering agent is the level of serum potassium, the ion decisive for resting membrane potential and degree of excitability.