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.