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

Molecular Psychiatry volume 19, pages 573–579 (2014)Cite this article

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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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Acknowledgements

These studies were supported by NIMH (MH 062236 and MH 83957).

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Authors and Affiliations

  1. Department of Psychiatry, University of Texas Southwestern Medical School, Dallas, TX, USA

    M Yanagi, S A Southcott, A A Shukla, S Ghose & C A Tamminga

  2. Department of Neuroscience, University of Texas Southwestern Medical School, Dallas, TX, USA

    R H Joho

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Correspondence to C A Tamminga.

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3RH Joho is recently deceased.

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Yanagi, M., Joho, R., Southcott, S. et al. Kv3.1-containing K+ channels are reduced in untreated schizophrenia and normalized with antipsychotic drugs. Mol Psychiatry 19, 573–579 (2014). https://doi.org/10.1038/mp.2013.49

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