Sodium channel mutations in paramyotonia congenita exhibit similar biophysical phenotypes in vitro

Naibo Yang*, Sen Ji, Ming Zhou, Louis J. Ptáček, Robert L. Barchi, Richard Horn, Alfred L. George

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

169 Scopus citations

Abstract

Mutations in the skeletal muscle voltage-gated Na+ channel α-subunit have been found in patients with two distinct hereditary disorders of sarcolemmal excitation: hyperkalemic periodic paralysis (HYPP) and paramyotonia congenita (PC). Six of these mutations have been functionally expressed in a heterologous cell line (tsA201 cells) using the recombinant human skeletal muscle Na+ channel α-subunit cDNA hSkMI. PC mutants from diverse locations in this subunit (T1313M, L1433R, R1448H, R1448C, A1156T) all exhibit a similar disturbance in channel inactivation characterized by reduced macroscopic rate, accelerated recovery, and altered voltage dependence. PC mutants had no significant abnormality in activation. In contrast, one HYPP mutation studied (T704M) has a normal inactivation rate but exhibits shifts in the midpoints of steady-state activation and inactivation along the voltage axis. These findings help to explain the phenotypic differences between HYPP and PC at the molecular and biophysical level and contribute to our understanding of Na+ channel structure and function.

Original languageEnglish (US)
Pages (from-to)12785-12789
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number26
DOIs
StatePublished - Dec 20 1994

Keywords

  • electrophysiology
  • inactivation
  • myotonia
  • periodic paralysis

ASJC Scopus subject areas

  • General

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