Familial hypokalemic periodic paralysis is an autosomal-dominant channelopathy that features episodic attacks of flaccid paralysis with concomitant hypokalemia. Reduced activity of ATP-sensitive K+ (K-ATP) channels is suggested to be responsible for this disorder; however, the Molecular mechanisms have not yet been elucidated. In this study, we investigated the molecular mechanism of reduced K-ATP channel activity in skeletal muscle cells of patients with familial hypokalemic periodic paralysis We examined the mRNA and protein levels of SUR2A, a K-ATP, channel subunit. in cells from patients (patient cells) and normal individuals (normal cells). Our results demonstrated that normal cells exposed to 50 mM potassium buffer, which was used to induce depolarization, did not show significant change in the SUR2A mRNA levels; however, the protein level significantly increased in the cytosolic fraction. When the patient cells were exposed to 50 mM potassium buffer. the SUR2A mRNA level significantly decreased. Further, the protein level of SUR2A significantly increased in the membrane fraction but decreased in the cytosolic fraction in patient cells These findings suggest that abnormal localization of the SUR2A K+ channel protein leads to reduced K-ATP channel activity in familial hypokalemic periodic paralysis (C) 2009 Elsevier Inc. All rights reserved.