In patients with these mutations, the channel has a reduced excitability and signals from the central nervous system are unable to depolarise muscle.

The condition is hypokalemic because a low extracellular potassium ion concentration will cause the muscle to repolarise to the resting potential more quickly, so even if calcium conductance does occur it cannot be sustained.

[9][10] In hyperkalemic periodic paralysis, mutations occur in residues between transmembrane domains III and IV which make up the fast inactivation gate of Nav1.4.

Mutations have also been found on the cytoplasmic loops between the S4 and S5 helices of domains II, III and IV, which are the binding sites of the inactivation gate.

[10] The same types of mutations cause myotonia and paralysis, however the difference between these phenotypes depends on the level of sodium current that persists.