{
  "abstract": "MK-801, a phencyclidine (PCP) derivative also known as dizocilpine, is a potent noncompetitive antagonist of the N-Methyl-D-aspartate receptor (NMDAr). The NMDAr plays a critical role in mediating excitatory synaptic transmission in the central nervous system (CNS) and is important in regulating synaptic plasticity, learning, and memory. MK-801 is known to induce schizophrenia-like phenotypes in animal models by blocking the NMDAr. Several studies have reported that the cognitive impairment associated with schizophrenia is linked to functional defects of ion channels in parvalbumin-positive GABAergic interneurons. Kv3.1 is a voltage-gated K+ (Kv) channel involved in the rapid repolarization of the action potential in neurons; it is richly expressed in parvalbumin-positive GABAergic interneurons and is associated with fast, repetitive spike generation. A decrease of Kv3.1 in the CNS has been reported to be associated with schizophrenia. In the present study, the effect of MK-801 on Kv3.1 was investigated using the whole-cell patch-clamp technique in Chinese hamster ovary (CHO) cells stably expressing Kv3.1. MK-801 caused a concentration-dependent inhibition of Kv3.1, with an IC50 of 10.81 M and a Hill coefficient of 0.89. The blocking potency was stronger at depolarized potentials, indicating a voltage-dependent block. MK-801 also produced a use-dependent block, inducing progressive inhibition with repeated stimulation at increased frequencies (1 Hz and 2 Hz), consistent with a delay in recovery from inactivation of Kv3.1 in the presence of MK-801. In addition, MK-801 induced a hyperpolarizing shift in the voltage dependence of the steady-state inactivation curve of Kv3.1. Taken together, these results indicate that MK-801 blocks Kv3.1 expressed in CHO cells in a concentration-, voltage-, and state-dependent manner. Given the importance of Kv3.1 in parvalbumin-positive, fast-spiking GABAergic interneurons, these findings suggest that MK-801 may alter the firing patterns of these inhibitory neurons, contributing to the onset and symptoms of schizophrenia.",
  "abstract_shown": true,
  "affiliations": [
    "Konkuk University School of Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "T. J. Park"
    },
    {
      "name": "S. W. PARK"
    },
    {
      "name": "S. Park"
    },
    {
      "name": "Y. Lim"
    },
    {
      "name": "H. Lee"
    },
    {
      "name": "J. Kim"
    },
    {
      "name": "H. Kim"
    },
    {
      "name": "D. H. Kim"
    },
    {
      "name": "J. O-Uchi"
    },
    {
      "name": "M. S. Seo"
    },
    {
      "name": "J. R. An"
    },
    {
      "name": "B. H. Choi"
    },
    {
      "affs": [
        0
      ],
      "name": "Y. M. Bae"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c3n45qz89jdc1.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.06.749750",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.06.749750v1.full",
  "id": "c3n45qz89jdc1",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.06.749750v1",
  "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",
      "pharmacology and toxicology"
    ],
    [
      "openalex",
      "1312|Ion channel regulation and function"
    ]
  ],
  "openalex": "W7212786931",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.06.749750v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-06",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/c3n45qz89jdc1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:56Z",
      "native_id": "10.64898/2026.09.06.749750",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.06.749750v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:pharmacology and toxicology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Blockade of Kv3.1 by MK-801, a PCP-Derivative NMDA Receptor Inhibitor: Implications for Models of Schizophrenia",
  "title_text": "Blockade of Kv3.1 by MK-801, a PCP-Derivative NMDA Receptor Inhibitor: Implications for Models of Schizophrenia",
  "type": "preprint",
  "updated_at": "2026-10-30T12:21:56Z",
  "url": "https://research.draconitic.com/paper/c3n45qz89jdc1",
  "venue": "bioRxiv",
  "versions": []
}