Nav1.1 channels with mutations of severe myoclonic epilepsy in infancy display attenuated currents.
Severe myoclonic epilepsy in infancy (SMEI) is characterized by intractable febrile and afebrile seizures, severe mental decline, and onset during the first year of life. Nonsense, frameshift, and missense mutations of SCN1A gene encoding the voltage-gated Na(+) channel alpha-subunit type I (Na(v)1.1) have been identified in patients with SMEI. Here, we performed whole-cell patch-clamp analyses on HEK293 cells expressing human Na(v)1.1 channels bearing SMEI nonsense and missense mutations. The mutant channels showed remarkably attenuated or barely detectable inward sodium currents. Our findings indicate that SMEI mutations lead to loss-of-function and may contribute to the development of SMEI phenotypes.
Sugawara
Takashi
T
Laboratory for Neurogenetics, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Tsurubuchi
Yuji
Y
Fujiwara
Tateki
T
Mazaki-Miyazaki
Emi
E
Nagata
Keiichi
K
Montal
Mauricio
M
Inoue
Yushi
Y
Yamakawa
Kazuhiro
K
D002460:Cell Line; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D006801:Humans; D009154:Mutation; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics*
D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels