抄録
Over 30 missense mutations in human skeletal muscle Na channel (SCN4A) have been identified in families with either myotonia or periodic paralysis, or both. A 38-years-old woman with positive family history was manifested cold-aggravated myotonia without weakness from childhood. She was clinically diagnosed as potassium-aggravated myotonia, and screened SCN4A gene. A novel missense change of a residue located at intracellular C-terminal region (Q1633E) was identified. The functional effect of this mutation was assessed by recording whole-cell sodium currents from transiently transfected HEK293t cells using calcium phosphate method. Recordings were made with Axopatch 200B amplifier using pClamp 9 program. Fast inactivation was impaired for Q1633E channel, as demonstrated by approximately 10 mV rightwards shift in voltage dependence compared with wild type channel. There was no significant difference in the activation. We conclude that the observed defect of fast inactivation in mutant sodium channel leads myotonic symptom. Furthermore, our results suggest that the C-terminal region in SCN4A also plays an important role in fast inactivation. [J Physiol Sci. 2007;57 Suppl:S231]
