A New Potassium Channel on the Endoplasmic Reticulum Membrane in a Rat Brain: Electropharmacology and Molecular Evidence Publisher



Nazari M ; Eliassi A ; Saghiri R ; Nikbakht F ; Fahanikbabaei J
Source: Basic and Clinical Neuroscience Published:2025

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. Copyright © 2025 The Author(s);