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December 20, 1994ViewOpen Access

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

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Population

Heterologous cell line expressing recombinant human skeletal muscle Na+ channel alpha-subunit cDNA hSkM1

Comparison

Expression of paramyotonia congenita mutations vs Expression of hyperkalemic periodic paralysis…

Design

Preclinical

Authors

NYNaibo YangBGI Group (China)SJShou‐Hua JiShanghai University of Electric PowerMZMin ZhouThe Ohio State University Wexner Medical Center

Discussion

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Implication

Distinct Na+ channel gating defects differentiate PC from HYPP; extends mechanistic mapping of channelopathies but leaves open clinical translation.

Key Points

  • Characterize and compare the biophysical phenotypes of sodium channel alpha-subunit mutations responsible for paramyotonia congenita and hyperkalemic periodic paralysis.
  • Expressed recombinant human skeletal muscle voltage-gated Na+ channel alpha-subunit (hSkM1) cDNA in tsA201 cells.
  • Assessed electrophysiological properties of five paramyotonia congenita mutants (T1313M, L1433R, R1448H, R1448C, A1156T) and one hyperkalemic periodic paralysis mutant (T704M).
  • Paramyotonia congenita mutations consistently exhibited defective inactivation, characterized by reduced macroscopic inactivation rates, accelerated recovery, and altered voltage dependence without activation abnormalities.
  • The hyperkalemic periodic paralysis mutation (T704M) showed a normal rate of inactivation but shifted the midpoints of steady-state activation and inactivation along the voltage axis.

Structured PICO

P
Population
Heterologous cell line (tsA201 cells) expressing recombinant human skeletal muscle Na+ channel alpha-subunit cDNA hSkM1
I
Intervention
Expression of paramyotonia congenita (PC) mutations (T1313M, L1433R, R1448H, R1448C, A1156T)
C
Comparator
Expression of hyperkalemic periodic paralysis (HYPP) mutation (T704M)
O
Outcome
Channel inactivation and activation characteristics (macroscopic rate, recovery, voltage dependence)surrogate

Paramyotonia congenita and hyperkalemic periodic paralysis mutations in skeletal muscle sodium channels exhibit distinct biophysical phenotypes in vitro, explaining their phenotypic differences.

Cite This Study

Yang et al. (1994) studied this question.

synapsesocial.com/papers/6a70a2f0ac440176ef294d95https://doi.org/10.1073/pnas.91.26.12785
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Also Consider

Synapse has enriched 3 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Paramyotonia congenita and hyperkalemic periodic paralysis are linked to the adult muscle sodium channel gene1991 · 105 citations
  2. 2Primary structure of the adult human skeletal muscle voltage‐dependent sodium channel1992 · 181 citations
  3. 3Membrane defects in paramyotonia congenita (eulenburg)1987 · 107 citations