{
  "id": 11064811,
  "title": "Acute ClC-2 blockade increases neuronal intracellular chloride and depolarizes EGABA",
  "url": "https://urgent.news/2026/09/30/acute-clc-2-blockade-increases-neuronal-intracellular-chloride-and",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-30T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.24.753897v1?rss=1"
  },
  "original_language": "en",
  "account": "Neuronal intracellular chloride levels influence the polarity and effectiveness of GABA receptors in inhibiting neurons. ClC-2 is a channel that allows chloride to leave cells, but how it directly impacts EGABA and overall chloride balance in neurons is not fully understood. Researchers used a drug called AK-42, which specifically blocks ClC-2, to investigate its effects on GABAergic chloride signaling in brain tissue slices. They combined a technique called optogenetics to stimulate specific inhibitory nerve cells with a light-sensitive protein, measured the electrical signals produced in response, and measured chloride levels inside cells. AK-42 caused the electrical signals to become less negative (depolarized) compared to normal conditions, with this effect being more pronounced if the stimulation began 2 seconds after the cell's voltage was changed. This suggests that ClC-2 activity becomes more active over time when the cell's voltage is steady. AK-42 also stopped the more negatively charged electrical signals that typically occur after a 2-second stimulation delay, and it changed the baseline electrical activity without significantly altering the cell's resting state. Measurements taken with a special imaging technique showed that AK-42 caused an increase in chloride inside neurons even when another substance that blocks all chloride channels was present. Overall, these results demonstrate that blocking ClC-2 makes GABA signaling less negative, increases the amount of chloride inside neurons, and changes the timing of GABA's influence on neuron signaling, suggesting that ClC-2 plays an important role in quickly adjusting the chloride balance in nerve cells.",
  "summary": "Neuronal intracellular chloride concentration shapes the polarity and strength of GABAA receptor-mediated inhibition. ClC-2 is a hyperpolarization-activated chloride channel proposed to support chloride extrusion, but its acute contribution to EGABA and neuronal chloride homeostasis remains incompletely understood. Here, we used the selective ClC-2 inhibitor AK-42 to test how acute ClC-2…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}