Abnormal gating of axonal slow potassium current in cramp-fasciculation syndrome

作者：Shimatani Yoshimitsu; Nodera Hiroyuki^*; Shibuta Yoshiko; Miyazaki Yoshimichi; Misawa Sonoko; Kuwabara Satoshi; Kaji Ryuji

来源：Clinical Neurophysiology, 2015, 126(6): 1246-1254.

DOI：10.1016/j.clinph.2014.09.013

• Slow potassium channel
• Cramp
• Fasciculation
• Axonal excitability

Objective: Cramp-fasciculation syndrome (CFS) is a heterogeneous condition with multiple underlying causes. Although dysfunction of slow K+ channels has been reported in patients with CFS, testing all potential candidates for this problem using conventional in vitro functional analysis would be prohibitively cost-and labor-intensive. However, relatively economical and non-invasive nerve-excitability testing can identify ion channel dysfunction in vivo when combined with numerical modeling.
Methods: Patients with CFS underwent nerve conduction study, needle electromyography, and nerve excitability testing. Mathematical modeling of axonal properties was applied to identify the pathophysiology.
Results: Four patients had distinct electrophysiological findings (i.e., fasciculation potentials, doublet/multiplet motor unit potentials, and sustained F responses); excitability testing showed the following abnormalities: reduction of accommodation during prolonged depolarization, lack of late sub excitability after a supramaximal stimulation, and reduction of the strength-duration time constant. Mathematical modeling showed a loss of voltage-dependence of a slow K+ current. None of these patients had a mutation in the KCNQ2, 3, or 5 genes.
Conclusions: This study showed that patients with CFS might have abnormal kinetics in a slow K+ current.
Significance: Nerve-excitability testing may aid the decision to start therapeutic intervention such as administration of slow K+ channel openers.

• 出版日期2015-6