Open AccessActivation of ATP-sensitive potassium channels enhances DMT1-mediated iron uptake in SK-N-SH cells in vitro
Author(s) -
Xixun Du,
Huamin Xu,
Limin Shi,
Zhongg Jiang,
Ning Song,
Hong Jiang,
Junxia Xie
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep33674
Subject(s) - diazoxide , dmt1 , hyperpolarization (physics) , potassium channel , intracellular , chemistry , membrane potential , microbiology and biotechnology , biophysics , depolarization , glibenclamide , biochemistry , endocrinology , biology , transporter , insulin , organic chemistry , nuclear magnetic resonance spectroscopy , gene , diabetes mellitus
Iron importer divalent metal transporter 1 (DMT1) plays a crucial role in the nigal iron accumulation in Parkinson’s disease (PD). Membrane hyperpolarization is one of the factors that could affect its iron transport function. Besides iron, selective activation of the ATP-sensitive potassium (K ATP ) channels also contributes to the vulnerability of dopaminergic neurons in PD. Interestingly, activation of K ATP channels could induce membrane hyperpolarization. Therefore, it is of vital importance to study the effects of activation of K ATP channels on DMT1-mediated iron uptake function. In the present study, activation of K ATP channels by diazoxide resulted in the hyperpolarization of the membrane potential and increased DMT1-mediated iron uptake in SK-N-SH cells. This led to an increase in intracellular iron levels and a subsequent decrease in the mitochondrial membrane potential and an increase in ROS production. Delayed inactivation of the Fe 2+ -evoked currents by diazoxide was recorded by patch clamp in HEK293 cells, which demonstrated that diazoxide could prolonged DMT1-facilitated iron transport. While inhibition of K ATP channels by glibenclamide could block ferrous iron influx and the subsequent cell damage. Overexpression of Kir6.2/SUR1 resulted in an increase in iron influx and intracellular iron levels, which was markedly increased after diazoxide treatment.