{
  "abstract": "Aims: Seizure generation has been strongly linked to the accumulation of extracellular potassium. As astrocytes play a key role in potassium homeostasis, astrocyte targeted optogenetic modulation of extracellular potassium has been proposed as a novel strategy for seizure control. The effectiveness of such modulation is expected to depend strongly on the ion selectivity of the employed opsin. This study aims to mechanistically compare potassium-selective (WiChR) and cation-conducting (ChR2-like, ChR2*) opsins for astrocyte targeted modulation of extracellular potassium, and to determine how astrocytic properties and stimulation parameters influence modulation efficacy. Methods: A conductance-based computational framework was used to model astrocyte-extracellular space interactions, incorporating ion-specific photocurrents, Na+/K+-ATPase activity, and gap junction-mediated coupling within the astrocytic syncytium. Systematic parameter sweeps were performed to evaluate the influence of ion selectivity, astrocytic parameters, and stimulation paradigms on potassium dynamics. Results: WiChR-based modulation consistently produced more effective and robust reductions in [K+]e than ChR2*, via direct K+ inward currents and reduced dependence on pump activity. In contrast, ChR2* primarily limited potassium accumulation rather than reversing it and exhibited greater sensitivity to parameter variations, particularly Na+/K+-ATPase activity. The effectiveness of astrocyte-targeted modulation was strongly dependent on syncytial integrity, with reduced gap junction coupling impairing potassium clearance. Optimal stimulation performance for WiChR was observed for a pulse repetition period of 20 ms, with outcomes determined by the interaction between opsin kinetics and stimulation parameters. Conclusions: These results demonstrate that activation of WiChR opsins in astrocytes can reduce extracellular potassium levels and thereby modulate neuronal excitability. Ion selectivity emerges as a key determinant of modulation efficacy at the astrocytic level, with potassium-selective opsins providing a more direct and reliable approach than non-selective cation-conducting alternatives. Together, these findings establish a mechanistic basis for optogenetic activation of astrocytic potassium buffering as a potential strategy for seizure suppression and other neurological disorders associated with potassium dysregulation.",
  "abstract_shown": true,
  "affiliations": [
    "Ghent University: Universiteit Gent"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "L. Weyn"
    },
    {
      "name": "T. Tarnaud"
    },
    {
      "name": "W. Joseph"
    },
    {
      "name": "R. Raedt"
    },
    {
      "name": "E. Tanghe"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1efzcj8nev2d8.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.24.754075",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754075v1.full",
  "id": "1efzcj8nev2d8",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754075v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "2804|Photoreceptor and optogenetics research"
    ]
  ],
  "openalex": "W7214648431",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754075v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1efzcj8nev2d8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:51Z",
      "native_id": "10.64898/2026.09.24.754075",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754075v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Seizure control via astrocyte targeted optogenetic extracellular potassium modulation: computational analysis of K+ vs non-selective cation-conducting opsins",
  "title_text": "Seizure control via astrocyte targeted optogenetic extracellular potassium modulation: computational analysis of K+ vs non-selective cation-conducting opsins",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:51Z",
  "url": "https://research.draconitic.com/paper/1efzcj8nev2d8",
  "venue": "bioRxiv",
  "versions": []
}