title: Endoplasmic reticulum membrane potassium channel dysfunction in high fat diet induced stress in rat hepatocytes.
abstract: In a previous study we reported the presence of a large conductance K(+) channel in the membrane of endoplasmic reticulum (ER) from rat hepatocytes. The channel open probability (Po) appeared voltage dependent and reached to a minimum 0.2 at +50 mV. Channel activity in this case was found to be totally inhibited at ATP concentration 2.5 mM, glibenclamide 100 µM and tolbutamide 400 µM. Existing evidence indicates an impairment of endoplasmic reticulum functions in ER stress condition. Because ER potassium channels have been involved in several ER functions including cytoprotection, apoptosis and calcium homeostasis, a study was carried out to consider whether the ER potassium channel function is altered in a high fat diet model of ER stress. Male Wistar rats were made ER stress for 2 weeks with a high fat diet. Ion channel incorporation of ER stress model into the bilayer lipid membrane allowed the characterization of K(+) channel. Our results indicate that the channel Po was significantly increased at voltages above +30 mV. Interestingly, addition of ATP 7.5 mM, glibenclamide 400 µM and tolbutamide 2400 µM totally inhibited the channel activities, 3-fold, 4-fold and 6-fold higher than that in the control groups, respectively. Our results thus demonstrate a modification in the ER K(+) channel gating properties and decreased sensitivity to drugs in membrane preparations coming from ER high fat model of ER stress, an effect potentially linked to a change in ER K(+) channel subunits in ER stress condition. Our results may provide new insights into the cellular mechanisms underlying ER dysfunctions in ER stress.
authors.affiliation: Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Evin, Tehran 19857, Iran ; Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Evin, Tehran 19857, Iran.
authors.forename: Naser
authors.initials: N
authors.lastname: Khodaee
authors.affiliation: Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Evin, Tehran 19857, Iran ; Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Evin, Tehran 19857, Iran.
authors.forename: Maedeh
authors.initials: M
authors.lastname: Ghasemi
authors.affiliation: Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Saghiri
authors.affiliation: Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Evin, Tehran 19857, Iran ; Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Evin, Tehran 19857, Iran.
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Eliassi
keywords: ER stress; bilayer lipid membrane; endoplasmic reticulum; hepatocytes; potassium channel