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AB-2

A potassium channel, Kv3.1, is reduced in schizophrenia and normalized with antipsychotic drugs; a possible new drug target for schizophrenia

MASAYA YANAGI1, Rolf Joho2, Sarah Hendrix3, Abhay Shukla3, Subroto Ghose3, Carol Tamminga3

  1. Department of Neuropsychiatry, Kinki University School of Medicine,
  2. Department of Neuroscience, University of Texas Southwestern Medical Center,
  3. Department of Psychiatry, University of Texas Southwestern Medical Center
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. Kv3.1b, a major subtype of Kv3.1, and Kv3.2 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. In addition, postmortem brain studies have shown that the PV expression is decreased in prefrontal cortex of schizophrenia. We identified the distribution of Kv3.1b and Kv3.2 protein in normal human brain, showing that Kv3.1b is limited to neocortical Shukla creased in neocortex, but only in cases without antipsychotic drug (APD) treatment; Kv3.1 levels were normal in antipsychotic-treated cases. Kv3.2 was 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 schizophrenia 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 which 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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  1. Special Lecture
  2. NP Special Lecture
  3. Clinical Research Educational Seminar
  4. Symposiums
  5. Prize for encouragement of the society
  6. Abroad
  7. Lunceon Seminar
  8. Evening Seminar
  9. Oral Abstracts
  10. Poster Abstracts