A novel Kir2.6 mutation associated with hypokalemic periodic paralysis
| Autor: | Fuchen Liu, Chuanzhu Yan, Ying Hou, Jinfan Zheng, Zonglai Liang, Yuanyuan Hu, Pengfei Lin |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Nav1.4 Mutant Action Potentials Gene mutation 03 medical and health sciences 0302 clinical medicine Hypokalemic periodic paralysis Physiology (medical) Internal medicine Chlorocebus aethiops medicine Paralysis Animals Humans Patch clamp Potassium Channels Inwardly Rectifying biology Chemistry Wild type Thyrotoxic periodic paralysis medicine.disease Sensory Systems 030104 developmental biology Endocrinology HEK293 Cells Neurology COS Cells Mutation biology.protein Neurology (clinical) medicine.symptom Paralysis Hyperkalemic Periodic 030217 neurology & neurosurgery |
| Zdroj: | Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. 127(6) |
| ISSN: | 1872-8952 |
| Popis: | Background and objective Mutations in KCNJ18 , which encodes the inwardly rectifying potassium channel Kir2.6, have rarely been reported in hypokalemic periodic paralysis. We describe the clinical phenotype of a novel KCNJ18 gene mutation and perform functional characterization of this mutant Kir2.6. Methods A long-term exercise test (ET) was conducted based on the McManis method. Whole-cell currents were recorded using patch clamp, and the HEK293 cells were transfected with wild-type or/and mutant Kir2.6 cDNA. Results A de novo conserved heterozygous mutation in Kir2.6, G169R, was found in a hypokalemic periodic paralysis patient. ET led to a decrease in the amplitude of compound muscle action potential (CMAP) by 64%. Patch clamp results showed that the potassium inward and outward current densities of the G169R mutant were, respectively, reduced by 65.6% and 84.7%; for co-expression with wild type, which more closely resembles the physiological conditions in vitro, the inward and outward current densities decreased, respectively, by 48.2% and 47.4%. Conclusions A novel KCNJ18 mutation, G169R, was first reported to be associated with hypokalemic periodic paralysis without hyperthyroidism. Electrophysiological results demonstrated a significant functional defect of this mutant, which may predispose patients with this mutation to paralysis. Significance This new G169R mutation of the potassium channel Kir2.6 provides insight into the pathogenic mechanisms of hypokalemic periodic paralysis. |
| Databáze: | OpenAIRE |
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