Heide, Juliane and Mann, Stefan A and Vandenberg, Jamie I (2012) The schizophrenia-associated Kv11.1-3.1 isoform results in reduced current accumulation during repetitive brief depolarizations. PloS one, 7 (9). pp. e45624. ISSN 1932-6203 (Gold OA)
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Abstract
Recent genome wide association studies identified a brain and primate specific isoform of a voltage-gated potassium channel, referred to as Kv11.1-3.1, which is significantly associated with schizophrenia. The 3.1 isoform replaces the first 102 amino acids of the most abundant isoform (referred to as Kv11.1-1A) with six unique amino acids. Here we show that the Kv11.1-3.1 isoform has faster rates of channel deactivation but a slowing of the rates of inactivation compared to the Kv11.1-1A isoform. The Kv11.1-3.1 isoform also has a significant depolarizing shift in the voltage-dependence of steady-state inactivation. The consequence of the altered gating kinetics is that there is lower current accumulation for Kv11.1-3.1 expressing cells during repetitive action potential firing compared to Kv11.1-1A expressing cells, which in turn will result in longer lasting trains of action potentials. Increased expression of Kv11.1-3.1 channels in the brain of schizophrenia patients might therefore contribute to disorganized neuronal firing.
(Schizophrenia Research Institute, St. Vincent’s Clinic Foundation, and NHMRC grant 1019693) (http://www.nhmrc.gov.au/).
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 18 Dec 2015 05:42 |
| Last Modified: | 22 Jan 2016 03:09 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/16 |
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