Published online Dec 19, 2019. doi: 10.5493/wjem.v9.i2.14
Peer-review started: May 20, 2019
First decision: August 2, 2019
Revised: September 5, 2019
Accepted: November 20, 2019
Article in press: November 20, 2019
Published online: December 19, 2019
Processing time: 215 Days and 5.6 Hours
ATP-sensitive K+ (KATP) channels coupling nutrient metabolism to membrane potential are sensitive to intracellular ATP concentrations and ATP/ADP ratios. KATP channels are hetero-octameric in composition, formed by four pore-forming subunits including Kir6.1 and Kir6.2, which belong to the inward rectifying potassium channel family, and four regulatory subunits, SUR1, SUR2A and SUR2B, which belong to members of the ATP-binding cassette protein family. KATP channels were considered to be involved in cellular functions, such as pancreatic β cell secretion, muscle and neuronal excitability, and so on.
How KATP channels work in liver hepatocytes and sinusoidal cells is important to help understand liver function under normal and injury conditions. The first step is to characterize the localization and distribution of KATP channel subunits in different cells of the liver. This research focused on the localization and distribution of KATP channel subunits in hepatocytes and sinusoidal cells of rat liver. This research will provide the basic data to guide further research in medicine exploitation and clinical treatment for related liver diseases.
To investigate the expression of KATP channel subunits in rat liver and their localization in different cells of the liver.
In order to obtain basic knowledge of KATP channel subunits in rat liver distribution and localization, extracted liver protein was used for immunoblot analysis, cryosections of liver were used for immunohistochemistry, and primary cultured hepatic stellate cells (HSCs) and Kupffer cells were used for immunocytochemistry.
In the present study, five types of KATP channel subunits, including Kir6.1, Kir6.2, SUR1, SUR2A and SUR2B, were expressed in rat liver as revealed by immunoblot analysis and immunohistochemistry. Double immunofluorescence staining of cryosections, primary cultured HSCs and Kupffer cells showed that not only hepatocytes, but also HSCs, Kupffer cells and sinusoidal endothelial cells (SECs) contain KATP channel subunits.
The present study revealed that KATP channel subunits are expressed in rat liver, which is the first report that HSCs, Kupffer cells, and SECs contain KATP channel subunits formed by Kir6.1/SUR1, Kir6.1/SUR2A, Kir6.1/SUR2B, Kir6.2/SUR1, Kir6.2/SUR2A, and Kir6.2/SUR2B. Different combinations of KATP channels have different physiological and pharmacological characteristics. Thus, this research will supply basic experimental data to guide further exploration of liver function under normal and injury conditions.
In the present study, all experiments were performed under normal conditions. Thus, further study is needed to elucidate changes in KATP channel subunit composition under different metabolic states, including ischemia and hypoxia in vitro and/or in vivo with the use of KATP channel openers and blockers, such as diazoxide, pinacidil, glibenclamide, and tolbutamide.