Functional analysis of human Na+/K+-ATPase familial or sporadic hemiplegic migraine mutations expressed in Xenopus oocytes

Core Tip

Core tip: Mutations of the human ATP1A2 gene, which encodes the Na⁺/K⁺-ATPase α₂-subunit, are associated with familial hemiplegic migraine (FHM2) that is inherited in an autosomal dominant fashion. We studied seven ATP1A2 mutations related to FHM2 or sporadic hemiplegic migraine by electrophysiological and biochemical methods to characterize functional impairments. The mutations G855R, G900R, E902K, L994del, D999H, K1003E and Y1009X were selected according to their structural importance: in putative interaction sites between α- and β-subunit and in the α-subunit’s C-terminal region. Some of these mutations showed a severe loss of function, and we discuss the functional and physiological consequences in order to better understand the molecular basis for neurological impairments.