Kv3.1-containing K channels are reduced in untreated schizophrenia and normalized with antipsychotic drugs

Yanagi, M; Joho, R H; Southcott, S A; Shukla, A A; Ghose, S; Tamminga, C A

doi:10.1038/mp.2013.49

Cited by 106Schizophrenia research and treatmentIon channel regulation and functionNeuroscience and Neuropharmacology Research

Kv3.1-containing K channels are reduced in untreated schizophrenia and normalized with antipsychotic drugs

Yanagi, M, Joho, R H, Southcott, S A, Shukla, A A, Ghose, S, Tamminga, C A·2014·Molecular Psychiatry

DOI 10.1038/mp.2013.49

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Abstract

Neuronal firing is a fundamental element of cerebral function; and, voltage-gated potassium (K(+)) channels regulate that firing through the repolarization of action potentials. Kv3-type channels (Kv3.1-Kv3.4) represent a family of voltage-gated K(+) channels that have fast-spiking properties. Kv3.1 channel subunits are predominantly localized to cortical parvalbumin (PV)-positive, inhibitory interneurons. The firing properties of these interneurons participate in establishing the normal gamma oscillations and synchrony of cortical neuronal populations, thought to be the signature of higher information processing in human brain. Schizophrenia (SZ) is associated with abnormalities in cortical gamma synchrony and in information processing, particularly with dysfunction in working memory and executive function. Here, we report the distribution of Kv3.1b and Kv3.2 protein in normal human brain, showing that Kv3.1b is limited to neocortical areas, whereas Kv3.2 is abundantly represented in neo- and subcortical regions. In SZ cases, levels of Kv3.1b protein are decreased in the neocortex, but only in cases without antipsychotic drug (APD) treatment; Kv3.1 levels are normal in antipsychotic-treated cases. Kv3.2 is not different in distribution or in level between normal and SZ cases, nor influenced by APD, in any region tested. The apparent increase in Kv3.1b protein levels by APDs in SZ neocortex was confirmed in laboratory rodents treated with chronic APDs. These findings show a decrease in Kv3.1b channel protein in SZ neocortex, a deficit that is restored by APDs. This alteration could be fundamentally involved in the cortical manifestations of SZ and in the therapeutic response to APDs.

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Translational Neuroscience in Autism
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Identification, structural, and biophysical characterization of a positive modulator of human Kv3.1 channels
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A cytoskeleton-membrane interaction conserved in fast-spiking neurons controls movement, emotion, and memory
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Identification and characterization of site‐specific N‐glycosylation in the potassium channel Kv3.1b
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Dysfunctional Parvalbumin Neurons in Schizophrenia and the Pathway to the Clinical Application of Kv3 Channel Modulators
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Pharmacological modulation of Kv3 voltage-gated potassium channels regulates fear discrimination and expression in a response-dependent manner
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The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance
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Kv3.1 Voltage-gated Potassium Channels Modulate Anxiety-like Behaviors in Female Mice
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First Evidence of Kv3.1b Potassium Channel Subtype Expression during Neuronal Serotonergic 1C11 Cell Line Development
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A general pattern of non-spiking neuron dynamics under the effect of potassium and calcium channel modifications
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Hippocampal phase precession is preserved under ketamine, but the range of precession across a theta cycle is reduced
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Implication du canal potassium Kv3.1 dans la lipotoxicité du 7-cétocholestérol, 24S-hydroxycholestérol et de l’acide tétracosanoïque sur des cellules nerveuses 158N et BV-2 : Etude des relations entre Kv3.1, homéostasie potassique et métabolisme peroxysomal dans la maladie d’Alzheimer
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Correction of disorders of neuronal homeostatic mechanisms in case of neuropsychiatric diseases as a probable direction of drug exposure
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The new molecular targets for antidepressants
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Application of Evoked Response Audiometry To Schizophrenia For Specifying 40-Hz Aberrant Gamma Oscillations In A Real-World Clinical SettingPreprint
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Dysfunctional parvalbumin interneurons in a genetic mouse model of schizophreniaPreprint
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Additional file 20 of The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance
Que, T., Wang, H., Yang, W., Wu, J., Hou, C., Pei, S., Wu, Q., Li, L. M., Wei, S., Xie, X., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14391360
Additional file 19 of The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance
Que, T., Wang, H., Yang, W., Wu, J., Hou, C., Pei, S., Wu, Q., Li, L. M., Wei, S., Xie, X., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14391354
Additional file 18 of The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance
Que, T., Wang, H., Yang, W., Wu, J., Hou, C., Pei, S., Wu, Q., Li, L. M., Wei, S., Xie, X., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14391351
Additional file 21 of The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance
Que, T., Wang, H., Yang, W., Wu, J., Hou, C., Pei, S., Wu, Q., Li, L. M., Wei, S., Xie, X., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14391363
A theory on prefrontal dysfunction contributing to psychosis and other schizophrenia symptoms mediated by open potassium and hyperpolarization-activated cyclic nucleotide-gated channels
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Additional file 15 of The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance
Que, T., Wang, H., Yang, W., Wu, J., Hou, C., Pei, S., Wu, Q., Li, L. M., Wei, S., Xie, X., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14391342
Additional file 12 of The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance
Que, T., Wang, H., Yang, W., Wu, J., Hou, C., Pei, S., Wu, Q., Li, L. M., Wei, S., Xie, X., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14391333
Additional file 9 of The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance
阙腾程, Wang, H., Yang, W., Wu, J., Hou, C., Pei, S., Wu, Q., Li, L. M., Wei, S., Xie, X., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14391393
Additional file 3 of The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance
Que, T., Wang, H., Yang, W., Wu, J., Hou, C., Pei, S., Wu, Q., Li, L. M., Wei, S., Xie, X., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14391375
Additional file 10 of The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance
Que, T., Wang, H., Yang, W., Wu, J., Hou, C., Pei, S., Wu, Q., Li, L. M., Wei, S., Xie, X., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14391327
Additional file 17 of The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance
Que, T., Wang, H., Yang, W., Wu, J., Hou, C., Pei, S., Wu, Q., Li, L. M., Wei, S., Xie, X., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14391348
Additional file 23 of The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance
Que, T., Wang, H., Yang, W., Wu, J., Hou, C., Pei, S., Wu, Q., Li, L. M., Wei, S., Xie, X., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14391369
Additional file 2 of The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance
Que, T., Wang, H., Yang, W., Wu, J., Hou, C., Pei, S., Wu, Q., Li, L. M., Wei, S., Xie, X., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14391372
Additional file 5 of The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance
Que, T., Wang, H., Yang, W., Wu, J., Hou, C., Pei, S., Wu, Q., Li, L. M., Wei, S., Xie, X., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14391381
Additional file 7 of The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance
Que, T., Wang, H., Yang, W., Wu, J., Hou, C., Pei, S., Wu, Q., Li, L. M., Wei, S., Xie, X., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14391387
Additional file 6 of The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance
Que, T., Wang, H., Yang, W., Wu, J., Hou, C., Pei, S., Wu, Q., Li, L. M., Wei, S., Xie, X., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14391384
Additional file 11 of The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance
Que, T., Wang, H., Yang, W., Wu, J., Hou, C., Pei, S., Wu, Q., Li, L. M., Wei, S., Xie, X., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14391330
Additional file 14 of The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance
Que, T., Wang, H., Yang, W., Wu, J., Hou, C., Pei, S., Wu, Q., Li, L. M., Wei, S., Xie, X., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14391339
Additional file 1 of The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance
Que, T., Wang, H., Yang, W., Wu, J., Hou, C., Pei, S., Wu, Q., Li, L. M., Wei, S., Xie, X., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14391357
Additional file 22 of The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance
Que, T., Wang, H., Yang, W., Wu, J., Hou, C., Pei, S., Wu, Q., Li, L. M., Wei, S., Xie, X., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14391366
Additional file 4 of The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance
Que, T., Wang, H., Yang, W., Wu, J., Hou, C., Pei, S., Wu, Q., Li, L. M., Wei, S., Xie, X., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14391378

Dysfunctional Parvalbumin Neurons in Schizophrenia and the Pathway to the Clinical Application of Kv3 Channel Modulators
Yanagi, M., & Hashimoto, M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25168696 · Cited by 7 · see citing works
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3.3 Entraining Neural Networks Through Parvalbumin-Positive Interneurons: Can This Offer a Better way to Treat Schizophrenia?
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Kcns3 deficiency disrupts Parvalbumin neuron physiology in mouse prefrontal cortex: Implications for the pathophysiology of schizophrenia
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Lower gene expression for KCNS3 potassium channel subunit in parvalbumin-containing neurons in the prefrontal cortex in schizophrenia
Georgiev, D., Arion, D., Enwright, J. F., Kikuchi, M., Minabe, Y., Corradi, J. P., Lewis, D. A., & Hashimoto, T. (2014) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2013.13040468 · Cited by 61 · see citing works
Role of KCNH2 potassium channels in the pathogenesis of schizophrenia
Heide, J. (2022) · UNSWorks (UNSW Sydney) · doi:10.26190/unsworks/16316

Authors: Yanagi, M., Joho, R. H., Southcott, S. A., Shukla, A. A., Ghose, S., & Tamminga, C. A.
Affiliations: The University of Texas Southwestern Medical Center (US)
Corresponding author: Tamminga, C A
ORCID: Yanagi, M
Tamminga, C A
Venue: Molecular Psychiatry
Publisher: Springer Science and Business Media LLC
Published: 2013-04-30
Volume: 19
Issue: 5
Pages: 573-579
ISSN: 1359-4184 (ISSN-L)
1476-5578
DOI: 10.1038/mp.2013.49
OpenAlex: W2018625865
Cited by: 102
References: 49
Citations by year: 2026: 3 · 2025: 7 · 2024: 9 · 2023: 10 · 2022: 7 · 2021: 26 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 11 · 2016: 5 · 2015: 7 · 2014: 4 · 2013: 1
FWCI: 4.03
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Molecular Psychiatry (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Mental Health (MH062236, R01MH083957, MH 83957, R01MH062236)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: voltage-gated potassium channels, schizophrenia, antipsychotic drugs, parvalbumin interneurons, neocortex, gamma oscillations, neuronal firing, treatment response, chronic antipsychotic treatment, rodent models
MeSH terms: Animals, Brain, Haloperidol, Humans, RNA, Messenger, Schizophrenia, Antipsychotic Agents, Cohort Studies, Treatment Outcome, Risperidone, Neocortex, Rats, Shaw Potassium Channels

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Kv3.1-containing K channels are reduced in untreated schizophrenia and normalized with antipsychotic drugs

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