Altered gating and conductance of Na+ channels in hyperkalemic periodic paralysis.
Electrophysiological studies on muscle fibres from patients with hyperkalemic periodic paralysis with myotonia have shown that the episodes of weakness are caused by a sustained depolarization of the sarcolemma to potentials between -40 and -60 mV. In muscle fibre segments from three such patients this sustained depolarization was caused by noninactivating Na+ channels with reduced single-channel conductance blocked by TTX and procainamide. As the chloride conductance was normal, myotonia may be best explained with the abnormal reopenings of the Na+ channels. The recently described genetic linkage between hyperkalemic periodic paralysis with myotonia and the gene coding for the TTX-sensitive Na+ channel suggests an altered primary structure of this channel causing its abnormal function.
Lehmann-Horn
F
F
Neurologische Klinik, Technischen Universität München, Federal Republic of Germany.
Iaizzo
P A
PA
Hatt
H
H
Franke
C
C
D004553:Electric Conductivity; D006801:Humans; D006947:Hyperkalemia / Q000150:complications / Q000503:physiopathology*; D015640:Ion Channel Gating / Q000502:physiology*; D008564:Membrane Potentials; D009132:Muscles / Q000503:physiopathology*; D010245:Paralyses, Familial Periodic / Q000150:complications / Q000503:physiopathology*; D011342:Procainamide / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D015222:Sodium Channels; D013779:Tetrodotoxin; D011342:Procainamide