Unveiling Ketamine's Influence on Astrocytic Kir4.1 Channels Through Multimodal Analysis: Confocal Microscopy, Immunocytochemistry, Fluorescence Analysis, and Electrophysiology.
Samo Pirnat, Katja Fink, Matjaž Stenovec, Marko Kreft, Robert Zorec
Methods in molecular biology (Clifton, N.J.) 2025 DOI: 10.1007/978-1-0716-4366-2_20 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Multifaceted investigation Peer reviewed |
|---|---|
| Population | Cultured rat and mouse cortical astrocytes |
| Intervention | Ketamine |
| Topics | Ketamine Esketamine |
| Keywords | Astrocytes Confocal microscopy Electrophysiology Kir4.1 Vesicle mobility Depression treatment Psychopharmacology Cellular biology Brain research |
| Key points | Ketamine modulates the dynamics, surface density, and voltage-activated currents of the Kir4.1 potassium channel in astrocytes. |
Abstract
Understanding the elusive mechanisms responsible for the therapeutic efficacy of ketamine in major depressive disorder (MDD) is crucial. Astrocytes play a vital role in regulating extracellular potassium concentration ([K+]o), which is essential for maintaining proper neuronal excitability and overall brain function. Dysregulation of [K+]o can lead to significant changes in neuronal activity, potentially contributing to the pathophysiology of various neurological and psychiatric conditions, including depression. To this end, we conducted a multifaceted investigation to elucidate the effects of ketamine on the inwardly rectifying K+ channel Kir4.1, which is critical for neuronal excitability and K+ homeostasis. Using cultured rat cortical astrocytes expressing fluorescently labeled Kir4.1 (Kir4.1-EGFP), we followed the dynamics of Kir4.1-EGFP vesicles after ketamine exposure. In addition, using live cell immunolabeling and patch-clamp assays in cultured mouse astrocytes, we investigated the effects of ketamine on Kir4.1 surface density and voltage-activated currents, similar to Ba2+ inhibition. This comprehensive methodological approach sheds light on the modulation of Kir4.1 dynamics by ketamine and thus provides valuable insights into its therapeutic mechanisms in MDD.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cites 3
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression American Journal of Psychiatry October 1, 2015
- Ketamine Reduces the Surface Density of the Astroglial Kir4.1 Channel and Inhibits Voltage-Activated Currents in a Manner Similar to the Action of Ba2+ on K+ Currents. Cells May 10, 2023