Sodium channelopathies of skeletal muscle result from gain or loss of function.
Five hereditary sodium channelopathies of skeletal muscle have been identified. Prominent symptoms are either myotonia or weakness caused by an increase or decrease of muscle fiber excitability. The voltage-gated sodium channel NaV1.4, initiator of the muscle action potential, is mutated in all five disorders. Pathogenetically, both loss and gain of function mutations have been described, the latter being the more frequent mechanism and involving not just the ion-conducting pore, but aberrant pores as well. The type of channel malfunction is decisive for therapy which consists either of exerting a direct effect on the sodium channel, i.e., by blocking the pore, or of restoring skeletal muscle membrane potential to reduce the fraction of inactivated channels.
Institute of Applied Physiology, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
Karin
K
Jurkat-Rott
Boris
B
Holzherr
Michael
M
Fauler
Frank
F
Lehmann-Horn
D000200:Action Potentials / Q000502:physiology; D053447:Channelopathies / Q000235:genetics*; D006801:Humans; D020514:Hypokalemic Periodic Paralysis / Q000503:physiopathology; D008564:Membrane Potentials / Q000502:physiology; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism; D020967:Myotonic Disorders / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D062553:NAV1.4 Voltage-Gated Sodium Channel; D020513:Paralysis, Hyperkalemic Periodic / Q000503:physiopathology; D011188:Potassium / Q000009:adverse effects; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics* / Q000502:physiology
D009124:Muscle Proteins; D062553:NAV1.4 Voltage-Gated Sodium Channel; C106251:SCN4A protein, human; D015222:Sodium Channels; D011188:Potassium