RESUMO
OBJECTIVES: Acquired neuromyotonia (ANM) is an autoimmune disorder caused by antibodies to voltage-gated potassium channels (VGKC). Previously, we reported a patient with immunoglobulin M (IgM), instead of immunoglobulin G (IgG), anti-VGKC antibody. The purpose of this study was to determine the function of IgM-containing fraction in ANM patients. MATERIALS AND METHODS: We determined whether anti-VGKC antibodies in the IgG or IgM-containing fractions suppressed outward potassium current (OKC) using the patch clamp method in three patients with ANM. Whole sera from all patients suppressed OKCs. RESULT: Only the purified IgG, not the IgM-containing fractions from two patients suppressed VGKCs, whereas in a patient with IgM anti-VGKC antibody, only the IgM-containing fractions, not the IgG-containing fractions suppressed VGKCs. CONCLUSION: Anti-VGKC antibodies belonging to the IgM subclass should be determined in seronegative ANM patients.
Assuntos
Imunoglobulina M/análise , Síndrome de Isaacs/imunologia , Síndrome de Isaacs/fisiopatologia , Canais de Potássio de Abertura Dependente da Tensão da Membrana/imunologia , Canais de Potássio de Abertura Dependente da Tensão da Membrana/fisiologia , Formação de Anticorpos , Estudos de Casos e Controles , Humanos , Técnicas de Patch-ClampRESUMO
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.
Assuntos
Doenças do Sistema Nervoso Periférico/fisiopatologia , Canais de Potássio de Abertura Dependente da Tensão da Membrana , Canais de Potássio/fisiologia , Adolescente , Adulto , Idoso , Animais , Células CHO , Cricetinae , Canais de Potássio de Retificação Tardia , Feminino , Síndrome de Guillain-Barré/imunologia , Síndrome de Guillain-Barré/fisiopatologia , Humanos , Imunoglobulinas/imunologia , Imunoglobulinas/fisiologia , Ativação do Canal Iônico , Cinética , Canal de Potássio Kv1.1 , Masculino , Pessoa de Meia-Idade , Mioquimia/imunologia , Mioquimia/fisiopatologia , Miotonia/imunologia , Miotonia/fisiopatologia , Técnicas de Patch-Clamp , Doenças do Sistema Nervoso Periférico/imunologia , Canais de Potássio/metabolismo , Canais de Sódio/metabolismo , Canais de Sódio/fisiologia , Células Tumorais CultivadasRESUMO
We induced experimental myopathy in rabbits by giving simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor. After oral administration of simvastatin (50 mg/kg/day) for 2 weeks, serum CK was elevated in 5 of 7 rabbits; degenerating or necrotic fibers were seen in 3 rabbits. Using electromyography, myotonic discharges were found in the 2 rabbits examined. The combination of myotonic discharges, necrosis and raised serum CK levels suggests that the myopathy was induced by lesions of the muscle surface membrane.
