Brain, Vol. 122, No. 11, 2057-2066,
November 1999
© 1999 Oxford University Press
Invited review |
Potassium current suppression in patients with peripheral nerve hyperexcitability
1 Third Department of Internal Medicine, 2 Department of Neuropsychiatry and 3 Second Department of Physiology, Kagoshima University School of Medicine, Kagoshima, Japan and 4 Zentrum für Molekulare Neurobiologie, Universität Hamburg, Germany
Correspondence to:
Dr Tatsui Nagado, Third Department of Internal Medicine, Kagoshima University School of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan
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.
acquired neuromyotonia; voltage-gated K+ channel; hKv 1.1 and 1.6; K+ current suppression; whole-cell patch-clamp
CIDP = chronic inflammatory demyelinating polyradicuroneuropathy; IGM = idiopathic generalized myokymia; LEMS = Lambert-Eaton myasthenic syndrome; NB-1 = human neuroblastoma cell line 1; NGF = nerve growth factor; VGKC = voltage-gated K+ channel
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