ACQUIRED NEUROMYOTONIA - EVIDENCE FOR AUTOANTIBODIES DIRECTED AGAINSTK-NERVES( CHANNELS OF PERIPHERAL)

Acquired neuromyotonia is characterized by hyperexcitability of motor nerves leading to muscle twitching, cramps, and weakness. The symptoms may improve following plasma exchange, and injection of immunoglobuli n G (IgG) from 1 neuromyotonia patient into mice increased the resista nce of neuromuscular transmission to d-tubocurarine. Here we examine n erves and muscle in vitro from mice injected with plasma or purified I gG from G neuromyotonia patients or pooled control subjects, and cultu red dorsal root ganglion cells after treatment with IgG. Three of the patients had antibodies against human voltage-gated potassium channels labeled with I-125-alpha-dendrotoxin. The quantal release of acetylch oline (quantal content) at end-plates in diaphragms from mice treated with neuromyotonia IgG preparations was increased by 21% relative to c ontrol values (P = 0.0053). With one IgG preparation, the duration of the superficial peroneal nerve compound action currents was increased by 93% The dorsal root ganglion cells treated with this IgG showed a m arked increase in repetitive firing of action potentials. All effects were similar to those obtained with aminopyridines. We conclude that a t least some patients with acquired neuromyotonia have antibodies dire cted against aminopyridine- or alpha-dendrotoxin-sensitive K+ channels in motor and sensory neurons, and they are likely to be implicated in the disease process.