Rat skeletal muscle channels with the T698M mutation retained approximately 25% of maximal sodium current after prolonged depolarization, compared to less than 3% in wild-type channels.
The T698M mutation impairs slow inactivation of sodium channels, which likely contributes to the persistent currents and muscle paralysis seen in Hyperkalemic periodic paralysis.
Absolute Event Rate: 25% vs 3%
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.
Cummins et al. (1996) studied Hyperkalemic periodic paralysis (HyperPP). T698M mutation in rat skeletal muscle channels vs. Wild-type channels and F1304Q mutant was evaluated on Available sodium current after holding at -20 mV for 20 min followed by a 10-ms hyperpolarization. Rat skeletal muscle channels with the T698M mutation retained approximately 25% of maximal sodium current after prolonged depolarization, compared to less than 3% in wild-type channels.