New mutation of the Na channel in the severe form of potassium-aggravated myotonia.

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.

• Authors: Tomoya Kubota, Masanobu Kinoshita, Ryogen Sasaki, Futoshi Aoike, Masanori P Takahashi, Saburo Sakoda, Kazuhiko Hirose
• Journal: Muscle & nerve (Muscle Nerve) Vol. 39 Issue 5 Pg. 666-73 (May 2009) ISSN: 0148-639X [Print] United States
• PMID: 19347921 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Muscle Proteins
• NAV1.4 Voltage-Gated Sodium Channel
• SCN4A protein, human
• Sodium Channels
• Glutamine
• Glutamic Acid
• Adenosine Triphosphatases

Topics

• Adenosine Triphosphatases (metabolism)
• Adult
• Biophysics
• Cell Line, Transformed
• Child
• DNA Mutational Analysis (methods)
• Electric Stimulation (methods)
• Electromyography (methods)
• Family Health
• Female
• Glutamic Acid (genetics)
• Glutamine (genetics)
• Humans
• Ion Channel Gating (genetics)
• Japan (ethnology)
• Male
• Membrane Potentials (drug effects, genetics)
• Middle Aged
• Models, Molecular
• Muscle Proteins (genetics, metabolism)
• Muscle, Skeletal (metabolism, physiopathology)
• Mutagenesis, Site-Directed (methods)
• Mutation, Missense (genetics)
• Myotonic Disorders (genetics, pathology, physiopathology)
• NAV1.4 Voltage-Gated Sodium Channel
• Patch-Clamp Techniques
• Sodium Channels (genetics, metabolism)
• Transfection