Cummins T R, Sigworth F J
Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Biophys J. 1996 Jul;71(1):227-36. doi: 10.1016/S0006-3495(96)79219-6.
Hyperkalemic periodic paralysis (HyperPP) is a disorder in which current through Na+ channels causes a prolonged depolarization of skeletal muscle fibers, resulting in membrane inexcitability and muscle paralysis. Although HyperPP mutations can enhance persistent sodium currents, unaltered slow inactivation would effectively eliminate any sustained currents through the mutant channels. We now report that rat skeletal muscle channels containing the mutation T698M, which corresponds to the human T704M HyperPP mutation, recover very quickly from prolonged depolarizations. Even after holding at -20 mV for 20 min, approximately 25% of the maximal sodium current is available subsequent to a 10-ms hyperpolarization (-100 mV). Under the same conditions, recovery is less than 3% in wild-type channels and in the F1304Q mutant, which has impaired fast inactivation. This effect of the T698M mutation on slow inactivation, in combination with its effects on activation, is expected to result in persistent currents such as that seen in HyperPP muscle.
高钾性周期性麻痹（HyperPP）是一种疾病，其中通过钠离子通道的电流导致骨骼肌纤维长时间去极化，从而导致膜兴奋性丧失和肌肉麻痹。尽管HyperPP突变可增强持续性钠电流，但未改变的缓慢失活将有效地消除通过突变通道的任何持续电流。我们现在报告，含有对应于人类T704M HyperPP突变的T698M突变的大鼠骨骼肌通道，从长时间去极化中恢复得非常快。即使在-20 mV下保持20分钟后，在10毫秒超极化（-100 mV）后仍有约25%的最大钠电流可用。在相同条件下，野生型通道和快速失活受损的F1304Q突变体的恢复率不到3%。T698M突变对缓慢失活的这种影响，与其对激活的影响相结合，预计会导致持续性电流，如在HyperPP肌肉中所见。
