Scholarlink

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.

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Unveiling Ketamine’s Influence on Astrocytic Kir4.1 Channels Through Multimodal Analysis: Confocal Microscopy, Immunocytochemistry, Fluorescence Analysis, and Electrophysiology

  • 实验方案

  • 发表日期：

    2025年

查看全文
  • Samo Pirnat,
  • Katja Fink,
  • Matjaž Stenovec,
  • Marko Kreft,
  • Robert Zorec

摘要

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.