가족성 저칼륨성 주기성마비 환자의 골격근 세포내 Kir6.2의 발현 및 분포 양상

Abstract

Familial hypokalemic periodic paralysis (HOKPP) is an autosomal dominant disorder characterized by reversible flaccid paralysis and intermittent hypokalemia. Although it has been reported that decreased activity in the channels of the skeletal muscle cell membrane plays a role in the pathogenesis of HOKPP, a clear mechanism has not yet been established. This study aimed to investigate the molecular biological mechanism underlying the decreased activity of channels in the skeletal muscles of familial HOKPP patients by studying the levels of the channel subunit Kir6.2. We found that when cells obtained from healthy individuals (normal cells) and HOKPP patients (patient cells) were treated with 4 mM potassium buffer, there was no quantitative change in the KCNJ11 mRNA levels and no difference in the Kir6.2 protein expression in the cytosol and cell membrane. On the other hand, when 1 mM potassium buffer was used, normal cells showed decreased expression of KCNJ11 mRNA as well as decreased expression of Kir6.2 protein in the cell membrane. However, patient cells treated with the same buffer showed no quantitative change in the levels of KCNJ11 mRNA or in the levels of Kir6.2 protein in the cytosol and cell membrane. Thus, in HOKPP patients, the Kir6.2 protein cannot be transported from the cell membrane to the cytosol, leading to closure of the channels, induction of depolarization, and subsequently, to the paralytic symptoms observed in the patient. Our findings thus provide new insights into the pathogenesis of HOKPP.