The p. I141V mutation in SCN4A and SCN5A, as well as its homologous p. I136V mutation in SCN9A, are interesting examples of mutations that have been linked to inherited hyperexcitability myotonia, exercise-induced polymorphic ventricular arrhythmias and erythromelalgia, respectively.
What type of mutation in neuron ion channels would you predict could likely cause hyperexcitability?
Mice with loss-of-function mutations in NaV1.1 channels have severely impaired sodium currents and action potential firing in hippocampal GABAergic inhibitory neurons without detectable effect on the excitatory pyramidal neurons, which would cause hyperexcitability and contribute to seizures in SMEI.
What causes Channelopathy?
Channelopathies are diseases that develop because of defects in ion channels caused by either genetic or acquired factors (Fig. 1). Mutations in genes encoding ion channels, which impair channel function, are the most common cause of channelopathies.
