Impairment of slow inactivation as a common mechanism for periodic paralysis in DIIS4-S5

@article{Bendahhou2002ImpairmentOS,
  title={Impairment of slow inactivation as a common mechanism for periodic paralysis in DIIS4-S5},
  author={Sa{\"i}d Bendahhou and Theodore R. Cummins and Roger W. Kula and Y.-H. Fu and Louis J. Pt{\'a}{\vc}ek},
  journal={Neurology},
  year={2002},
  volume={58},
  pages={1266-1272}
}
Background Mutations in the human skeletal muscle sodium channels are associated with hyperKPP, hypoKPP, paramyotonia congenita, and potassium-aggravated myotonia. This article describes the clinical manifestations of a patient with hyperKPP carrying a mutation (L689I) occurring in the linker DIIS4-S5 and its functional expression in a mammalian system. Objective To correlate the clinical manifestations of hyperkalemic periodic paralysis (hyperKPP) with the functional expression of a sodium… 

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References

SHOWING 1-10 OF 32 REFERENCES

Activation and Inactivation of the Voltage-Gated Sodium Channel: Role of Segment S5 Revealed by a Novel Hyperkalaemic Periodic Paralysis Mutation

Results, showing that the I1495F and T704M hyperkalaemic periodic paralysis mutations both have profound effects on channel activation and fast–slow inactivation, suggest that the S5 segment maybe in a location where fast and slow inactivation converge.

A double mutation in families with periodic paralysis defines new aspects of sodium channel slow inactivation.

One allele with two novel mutations occurring simultaneously in the SCN4A gene, encoding the human skeletal muscle voltage-gated Na(+) channel, is identified, demonstrating that manifestation of HyperKPP does not necessarily require disruption of slow inactivation.

Hyperkalemic periodic paralysis M1592V mutation modifies activation in human skeletal muscle Na+ channel.

The functional properties of the M1592V mutant resemble those of the previously characterized HPP T704M mutant, both clinically similar phenotypes arise from mutations located at a distance from the putative voltage sensor of the channel.

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

  • N. YangS. Ji A. George
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1994
Findings help to explain the phenotypic differences between HYPP and PC at the molecular and biophysical level and contribute to the understanding of Na+ channel structure and function.

Defective slow inactivation of sodium channels contributes to familial periodic paralysis

SI is defective in a subset of mutant Na channels associated with episodic weakness (HyperPP or PMC) but remains intact for mutants studied so far that cause myotonia without weakness (PAM).

Sodium channel mutations in acetazolamide‐responsive myotonia congenita, paramyotonia congenita, and hyperkalemic periodic paralysis

This report summarizes the sodium channel mutation analysis in 25 families with hyperKPP and reports the putative disease-causing mutation in acetazolamide-responsiveMyotonia congenita, a related disease in which myotonia is worsened by potassium but in which episodic weakness does not occur.