title: Potassium current suppression in patients with peripheral nerve hyperexcitability.
abstract: Acquired neuromyotonia (Isaac's syndrome) is considered to be an autoimmune disease, and the pathomechanism of nerve hyperexcitability in this syndrome is correlated with anti-voltage-gated K(+) channel (VGKC) antibodies. The patch-clamp technique was used to investigate the effects of immunoglobulins from acquired neuromyotonia patients on VGKCs and voltage-gated Na(+) channels in a human neuroblastoma cell line (NB-1). K(+) currents were suppressed in cells that had been co-cultured with acquired neuromyotonia patients' immunoglobulin for 3 days but not for 1 day. The activation and inactivation kinetics of the outward K(+) currents were not altered by these immunoglobulins, nor did the immunoglobulins significantly affect the Na(+) currents. Myokymia or myokymic discharges, with peripheral nerve hyperexcitability, also occur in various neurological disorders such as Guillain-Barré syndrome and idiopathic generalized myokymia without pseudomyotonia. Immuno-globulins from patients with these diseases suppressed K(+) but not Na(+) currents. In addition, in hKv 1.1- and 1.6-transfected CHO (Chinese hamster ovary)-K1 cells, the expressed VGKCs were suppressed by sera from acquired neuromyotonia patients without a change in gating kinetics. Our findings indicate that nerve hyperexcitability is mainly associated with the suppression of voltage-gated K(+) currents with no change in gating kinetics, and that this suppression occurs not only in acquired neuromyotonia but also in Guillain-Barré syndrome and idiopathic generalized myokymia without pseudomyotonia.
authors.affiliation: Third Department of Internal Medicine, Kagoshima University School of Medicine, Kagoshima, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nagado
authors.forename: K
authors.initials: K
authors.lastname: Arimura
authors.forename: Y
authors.initials: Y
authors.lastname: Sonoda
authors.forename: A
authors.initials: A
authors.lastname: Kurono
authors.forename: Y
authors.initials: Y
authors.lastname: Horikiri
authors.forename: A
authors.initials: A
authors.lastname: Kameyama
authors.forename: M
authors.initials: M
authors.lastname: Kameyama
authors.forename: O
authors.initials: O
authors.lastname: Pongs
authors.forename: M
authors.initials: M
authors.lastname: Osame
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D051668:Delayed Rectifier Potassium Channels; D005260:Female; D020275:Guillain-Barre Syndrome / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology / Q000502:physiology; D015640:Ion Channel Gating; D007700:Kinetics; D051662:Kv1.1 Potassium Channel; D008297:Male; D008875:Middle Aged; D020385:Myokymia / Q000276:immunology / Q000503:physiopathology; D009222:Myotonia / Q000276:immunology / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D010523:Peripheral Nervous System Diseases / Q000276:immunology / Q000503:physiopathology*; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D015222:Sodium Channels / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D051668:Delayed Rectifier Potassium Channels; D007136:Immunoglobulins; C496946:KCNA1 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015222:Sodium Channels; D051662:Kv1.1 Potassium Channel