Moreover, voltage-clamp fluorescent recordings to observe the Nav1.4 VSDs revealed that DIII and DIV VSD immobilization is correlated with the onset of inactivation (Cha et al., 1999); some mutants in DIII VSD were shown to impair fast inactivation and cause channelopathies, e.g., a mutation of R1135H in DIII S4 of Nav1.4 significantly enhanced entry into inactivation and prolonged recovery to cause hypokalemia periodic paralysis (Groome et al., 2014). This evidence concerns the gene SCN4A and channelopathy.