Expression patterns of two potassium channel genes in skeletal muscle cells of patients with familial hypokalemic periodic paralysis

• Published in: Neurology India 2011-07, Vol.59 (4), p.527-531
• Main Authors: Kim, June-Bum, Lee, Gyung-Min, Kim, Sung-Jo, Yoon, Dong-Ho, Lee, Young-Hyuk
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Calcium Channels - genetics; Cells, Cultured; Familial periodic paralysis; Gene Expression Regulation - drug effects; Gene Expression Regulation - genetics; Genes; Genetic aspects; Humans; Hypokalemic Periodic Paralysis - genetics; Hypokalemic Periodic Paralysis - pathology; KCNQ Potassium Channels - genetics; KCNQ Potassium Channels - metabolism; KCNQ3 Potassium Channel - genetics; KCNQ3 Potassium Channel - metabolism; Muscle cells; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - metabolism; Muscular system; Mutation; Mutation - genetics; Physiological aspects; Potassium - pharmacology; Potassium channels; Proteins; Risk factors; RNA, Messenger - metabolism; Rodents
• ISSN: 0028-3886; 1998-4022
• DOI: 10.4103/0028-3886.84331

Familial hypokalemic periodic paralysis is an autosomal-dominant disorder characterized by episodic attacks of muscle weakness with hypokalemia. The combination of sarcolemmal depolarization and hypokalemia has been attributed to abnormalities of the potassium conductance governing the membrane potential; however, the molecular mechanism that causes hypokalemia has not yet been determined. To test the hypothesis that the expression patterns of delayed rectifier potassium channel genes in the skeletal muscle cells of patients with familial hypokalemic periodic paralysis differ from those in normal cells. We examined both mRNA and protein levels of two major delayed rectifier potassium channel genes KCNQ3 and KCNQ5 in the skeletal muscle cells from three patients with familial hypokalemic periodic paralysis and three healthy controls. When normal cells were exposed to 50 mM potassium buffer, which was used to induce depolarization, the KCNQ3 protein level significantly increased in the membrane fraction but decreased in the cytosolic fraction, whereas the opposite was true in patient cells. Abnormal subcellular distribution of the KCNQ3 protein was observed in patient cells. Our results suggest that the altered expression of KCNQ3 in patient cells exposed to high extracellular potassium levels could possibly hinder normal function of the channel protein. These findings may provide an important clue to understanding the molecular mechanism of familial hypokalemic periodic paralysis.