Chapter 8 Sodium channelopathies in skeletal muscle and brain

Abstract

Publisher Summary The first so called “channelopathies” identified were skeletal muscle diseases, myotonias, and hyperkalemic periodic paralysis (HyperPP) that are sodium or chloride channel disorders. In recent years, complementary genetic and electrophysiological investigations led to the continuously growing list of channelopathies. Beside skeletal muscle, the channelopathies affect other excitable tissues, such as heart muscle and the nervous system. Voltage gated sodium channels (VGSCs) are membrane spanning proteins, responsible for the initiation and propagation of action potentials, in nerve and muscle cells. This chapter discusses the pathophysiological concepts of the sodium channelopathies found in skeletal muscle and brain— namely, HyperPP, paramyotonia congenita (PC), potassium aggravated myotonia (PAM), hypokalemic periodic paralysis type 2 (HypoPP2), generalized epilepsy, with febrile seizures plus (GEFS + ), and severe myoclonic epilepsy of infancy (SMEI). HyperPP, PC, and PAM are gain-of-function sodium channelopathies of the skeletal muscle. The inactivation defect, common to all mutations, can fully explain the phenotypes of myotonia and/or paralysis via a slight or strong membrane depolarization, respectively. HypoPP2 is a loss-of-function sodium channelopathy, but the described enhancement of fast and/or slow inactivation can only explain a part of the pathophysiological features of this disease.