Reduced expression and abnormal localization of the K(ATP) channel subunit SUR2A in patients with familial hypokalemic periodic paralysis.
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 50mM 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 50mM 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.
Kim
Sung-Jo
SJ
Department of Biotechnology, Hoseo University, 165 Baebang-Myun, Asan, Chungnam, Republic of Korea.
Lee
Yea-Jin
YJ
Kim
June-Bum
JB
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D020514:Hypokalemic Periodic Paralysis / Q000378:metabolism* / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011955:Receptors, Drug / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064233:Sulfonylurea Receptors
C577510:ABCC9 protein, human; D018528:ATP-Binding Cassette Transporters; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors