The P1158S mutant SCN4A exhibited hyperpolarizing shifts in voltage dependence of activation and inactivation curves at cold temperatures and a slower rate of inactivation compared to wild-type.
Does the P1158S mutation in SCN4A cause temperature-dependent shifts in voltage dependence of sodium channel gating?
The P1158S mutation in SCN4A causes cold-induced hypokalemic periodic paralysis and myotonia through temperature-dependent hyperpolarizing shifts in voltage dependence of sodium channel gating.
BACKGROUND: The authors reported a mutation, P1158S, of the human skeletal muscle sodium channel gene (SCN4A) in a family with cold-induced hypokalemic periodic paralysis (hypoKPP) and myotonia. OBJECTIVE: To identify mechanisms of temperature dependency in this channelopathy. METHODS: Using the amphotericin B perforated patch clamp method, sodium currents were recorded at 22 and 32 degrees C from the wild-type (WT) and P1158S mutant SCN4A expressed in tsA201 cells. Computer simulation was performed, incorporating the gating parameters of the P1158S mutant SCN4A. RESULTS: P1158S mutant SCN4A exhibited hyperpolarizing shifts in voltage dependence of both activation and inactivation curves at a cold temperature and a slower rate of inactivation than the WT. Computer simulation reproduced the abnormal skeletal muscle electrical activities of both paralysis at a low potassium concentration in the cold and myotonia at a normal potassium concentration. CONCLUSIONS: Both paralysis and myotonia are attributable to the biophysical properties of the SCN4A mutation associated with hypoKPP. This is the first report of an SCN4A mutation that exhibits temperature-dependent shifts of voltage dependence in sodium channel gating.
Sugiura et al. (Tue,) conducted a other in Cold-induced hypokalemic periodic paralysis (hypoKPP) and myotonia. P1158S mutant SCN4A at cold temperature vs. Wild-type SCN4A and normal temperature was evaluated on Voltage dependence of activation and inactivation curves and rate of inactivation. The P1158S mutant SCN4A exhibited hyperpolarizing shifts in voltage dependence of activation and inactivation curves at cold temperatures and a slower rate of inactivation compared to wild-type.