Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Exp Med. Dec 19, 2019; 9(2): 14-31
Published online Dec 19, 2019. doi: 10.5493/wjem.v9.i2.14
Localization of ATP-sensitive K+ channel subunits in rat liver
Ming Zhou, Kiwamu Yoshikawa, Hideo Akashi, Mitsutaka Miura, Ryoji Suzuki, Tao-Sheng Li, Hiroshi Abe, Yoshio Bando
Ming Zhou, Hideo Akashi, Ryoji Suzuki, Yoshio Bando, Department of Anatomy, Akita University Graduate School of Medicine, Akita 010-8543, Japan
Kiwamu Yoshikawa, Mitsutaka Miura, Department of Cell Biology and Morphology, Akita University Graduate School of Medicine, Akita 010-8543, Japan
Tao-Sheng Li, Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki 852-8523, Japan
Hiroshi Abe, TRUST, A Long-Term Care Health Facility, Sendai 980-0011, Japan
Author contributions: Zhou M did the main experiments, collected the data, and wrote the paper; Yoshikawa K and Miura M performed the experiment of primary culture for hepatic stellate cells and Kupffer cells; Akashi H and Suzuki R participated in treatment of animals; Li TS, Abe H, and Bando Y supervised the investigation and approved the manuscript for publication.
Supported by the Program of the network-type joint Usage/Research Center for Radiation Disaster Medical Science of Hiroshima University, Nagasaki University, and Fukushima Medical University.
Institutional review board statement: This study was approved by the Animal Research Committee of Akita University.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Animal Research Committee of Akita University (a-1-2405).
Conflict-of-interest statement: Authors declare no conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Ming Zhou, MD, PhD, Assistant Professor, Department of Anatomy, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan. mzhou@med.akita-u.ac.jp
Telephone: +81-18-8846260 Fax: +81-18-8846440
Received: May 17, 2019
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
ARTICLE HIGHLIGHTS
Research background

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.

Research motivation

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.

Research objectives

To investigate the expression of KATP channel subunits in rat liver and their localization in different cells of the liver.

Research methods

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.

Research results

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.

Research conclusions

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.

Research perspectives

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.