Functional expression of sodium channel mutations identified in families with periodic paralysis.
Two mutations in the sodium channel alpha subunit that have been implicated as the cause of periodic paralysis were studied by functional expression in a mammalian cell line. Both mutations disrupted inactivation without affecting the time course of the onset of the sodium current or the single-channel conductance. This is the same functional defect that was observed in myotubes cultured from affected patients and proves that these mutations are not benign polymorphisms. Unlike the currents in the myotubes, however, there was no consistent potassium dependence for the noninactivating component. These mutations also define new regions of the sodium channel alpha subunit that are involved in the process of inactivation.
Department of Neurology, Howard Hughes Medical Institute, Massachusetts General Hospital, Boston 02114.
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Cannon
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Strittmatter
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004553:Electric Conductivity; D004594:Electrophysiology; D004622:Embryo, Mammalian; D015870:Gene Expression; D006801:Humans; D007668:Kidney; D007700:Kinetics; D008969:Molecular Sequence Data; D009132:Muscles / Q000503:physiopathology; D009154:Mutation; D010245:Paralyses, Familial Periodic / Q000235:genetics* / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D051381:Rats; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D014162:Transfection
D015222:Sodium Channels