Skeletal muscle na channel disorders

Abstract

Five inherited human disorders affecting skeletal muscle contraction have been traced to mutations in the gene encoding the voltage-gated sodium channel Na(v)1.4. The main symptoms of these disorders are myotonia or periodic paralysis caused by changes in skeletal muscle fiber excitability. Symptoms of these disorders vary from mild or latent disease to incapacitating or even death in severe cases. As new human sodium channel mutations corresponding to disease states become discovered, the importance of understanding the role of the sodium channel in skeletal muscle function and disease state grows.

Keywords: Nav1.4; skeletal muscle; sodium channel; treatment.

Figure 1

Basic structure of the voltage-gated sodium channel. Structural arrangement of the Na_v1.4 channel α-subunit which is organized into four homologous domains (I to IV) and possesses six transmembrane segments (S1–S6), a pore-forming loop located between S5 and S6 segments, and cytosolic NH₃ and COOH termini. The schematic diagram of the Na_v1.4 channel shows the location of the mutations associated with hyperkalemic periodic paralysis (HyperPP), hypokalemic periodic paralysis (HypoPP), normokalemic periodic paralysis (NormoPP), paramyotonia congenita (PMC), potassium-aggravated myotonia (PAM), cold-aggravated myotonia (CAM), and congenital myasthenic syndrome (CMS).