Nazari M, Eliassi A, Saghiri R, Nikbakht F, Fahanik-babaei J. A New Potassium Channel on the Endoplasmic Reticulum Membrane in a Rat Brain: Electropharmacology and Molecular Evidence. BCN 2025; 16 (6) :1017-1032
URL:
http://bcn.iums.ac.ir/article-1-2748-en.html
1- Department of Physiology, School of Medicine, Arak University of Medical Sciences, Arak, Iran.
2- Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. & Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
3- Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran.
4- Department of Physiology, Cellular and Molecular Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
5- Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Abstract:
Introduction: Several types of ion channels found in the plasma membrane have also been identified in the membranes of intracellular organelles. These ion channels, including potassium channels, play a crucial role in regulating intracellular ion homeostasis. An ATP-sensitive potassium (KATP) channel with various functional roles has been identified in the endo/sarcoplasmic reticulum membranes of both excitable and non-excitable cells. Our previous studies investigated the electropharmacological and molecular properties of KATP and BKCa+2 channels in the rough endoplasmic reticulum (RER) of rat hepatocytes.
Methods: In this study, for the first time, we described the electropharmacological and molecular properties of the RER KATP channel in rat brain cells using an incorporated single-channel in a planar lipid bilayer and Western blotting.
Results: The results of the study revealed the presence of a KATP channel with a conductance of 306 pS, and the open probability was found to be voltage-independent at holding potentials ranging from +40 to -60 in an asymmetric solution (200/50 mM KCl; cis/trans). Additionally, we observed that adding ATP (2.5 mM) to both positive and negative potentials, and 100 μM glibenclamide to the positive voltages inhibited channel activity. The addition of 100 mM 5-HD and 100 nM charybdotoxin to the cis side did not affect the channel behavior. Furthermore, a Western blot analysis provided evidence of the expression of Kir6.2, Kir6.1, sulfonylurea receptor (SUR)1, and/or SUR2B, but not SUR2A, in the RER of rat brain fractions.
Conclusion: In this study, we provide strong evidence for the existence of a KATP channel on the RER membrane of rat brain cells, displaying pharmacological properties distinct from those classically described for the plasma membrane and other intracellular organelles.
Type of Study:
Original |
Subject:
Cellular and molecular Neuroscience Received: 2023/07/15 | Accepted: 2024/04/13 | Published: 2025/11/28