title: Enhanced slow inactivation of the human skeletal muscle sodium channel causing normokalemic periodic paralysis.
abstract: Normokalemic periodic paralysis (normoPP) is a type of skeletal muscle function disorder which is characterized by paralysis attack with concomitant normal serum potassium level. We previously reported that R675Q mutation of human skeletal muscle voltage-gated sodium channel α subunit (SCN4A) may be the novel mutation which caused normoPP in Chinese families. However, it is still not clear how this mutation affects the SCN4A channel function. In this study, we used patch-clamp recording to study the function of wild type (WT) and R675Q mutant of SCN4A channels expressed in human embryonic kidney (HEK293) cells. We found that R675Q mutation did not affect the voltage dependence of sodium channel activation. The fast inactivation was also not significantly affected by R675Q mutation. However, R675Q mutation of SCN4A channels exhibited an 11.1 mV hyperpolarized shift in the voltage dependence of slow inactivation and significantly prolonged the recovery from prolonged inactivation state. Our results thus indicate that SCN4A was functionally affected by R675Q mutation, suggesting a possible reason for causing normoPP in Chinese patients.
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Medical School, Zhejiang University, Jiefang Road 88, Hangzhou, 310009, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wu
authors.forename: Baorong
authors.initials: B
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Kang
authors.forename: Weiping
authors.initials: W
authors.lastname: Wu
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D044466:Asian People / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D062553:NAV1.4 Voltage-Gated Sodium Channel / Q000502:physiology*; D010245:Paralyses, Familial Periodic / Q000235:genetics*; D026941:Sodium Channel Blockers / Q000494:pharmacology
chemical_list: D062553:NAV1.4 Voltage-Gated Sodium Channel; C106251:SCN4A protein, human; D026941:Sodium Channel Blockers