New mutation of the Na channel in the severe form of potassium-aggravated myotonia.
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Kubota T, Kinoshita M, Sasaki R, Aoike F, Takahashi MP, Sakoda S, Hirose K
New mutation of the Na channel in the severe form of potassium-aggravated myotonia.
Muscle Nerve. 2009 May;39(5):666-73. doi: 10.1002/mus.21155.
- PubMed ID
- 19347921 [ View in PubMed]
- Abstract
Myotonia manifests in several hereditary diseases, including hyperkalemic periodic paralysis (HyperPP), paramyotonia congenita (PMC), and potassium-aggravated myotonia (PAM). These are allelic disorders originating from missense mutations in the gene that codes the skeletal muscle sodium channel, Nav1.4. Moreover, a severe form of PAM has been designated as myotonia permanens. A new mutation of Nav1.4, Q1633E, was identified in a Japanese family presenting with the PAM phenotype. The proband suffered from cyanotic attacks during infancy. The mutated amino acid residue is located on the EF-hand calcium-binding motif in the intracellular C-terminus. A functional analysis of the mutant channel using the voltage-clamp method revealed disruption of fast inactivation, a slower rate of current decay, and a depolarized shift in the voltage dependence of availability. This study has identified a new mutation of PAM with a severe phenotype and emphasizes the importance of the C-terminus for fast inactivation of the sodium channel. Muscle Nerve 39: 666-673, 2009.