title: Kv3.1-containing K(+) channels are reduced in untreated schizophrenia and normalized with antipsychotic drugs.
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.
authors: Department of Psychiatry, University of Texas Southwestern Medical School, Dallas, TX, USA.
authors: M
authors: M
authors: Yanagi
authors: Department of Neuroscience, University of Texas Southwestern Medical School, Dallas, TX, USA.
authors: R H
authors: RH
authors: Joho
authors: Department of Psychiatry, University of Texas Southwestern Medical School, Dallas, TX, USA.
authors: S A
authors: SA
authors: Southcott
authors: Department of Psychiatry, University of Texas Southwestern Medical School, Dallas, TX, USA.
authors: A A
authors: AA
authors: Shukla
authors: Department of Psychiatry, University of Texas Southwestern Medical School, Dallas, TX, USA.
authors: S
authors: S
authors: Ghose
authors: Department of Psychiatry, University of Texas Southwestern Medical School, Dallas, TX, USA.
authors: C A
authors: CA
authors: Tamminga
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D015331:Cohort Studies; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D019579:Neocortex / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018967:Risperidone / Q000494:pharmacology; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism*; D051670:Shaw Potassium Channels / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; C489597:KCNC1 protein, human; C489596:KCNC2 protein, human; D012333:RNA, Messenger; D051670:Shaw Potassium Channels; D006220:Haloperidol; D018967:Risperidone
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