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. 1994 Dec 20;91(26):12785–12789. doi: 10.1073/pnas.91.26.12785

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

N Yang 1, S Ji 1, M Zhou 1, L J Ptácek 1, R L Barchi 1, R Horn 1, A L George Jr 1
PMCID: PMC45524  PMID: 7809121

Abstract

Mutations in the skeletal muscle voltage-gated Na+ channel alpha-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 alpha-subunit cDNA hSkM1. 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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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