SCN4A and Myotonia: In a recent study of a gain-of-function mutation (M1476I) in NaV1.4 (Zhao et al., 2012), which is associated with cold-induced myotonia, effects on channel gating properties were also observed, although mexiletine significantly shifted the voltage-dependent activation and inactivation curves of both WT and M1476I channels in a hyperpolarizing direction.