title: The schizophrenia-associated Kv11.1-3.1 isoform results in reduced current accumulation during repetitive brief depolarizations.
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.
authors.affiliation: Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia.
authors.forename: Juliane
authors.initials: J
authors.lastname: Heide
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Mann
authors.forename: Jamie I
authors.initials: JI
authors.lastname: Vandenberg
mesh_terms: D000200:Action Potentials; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D017931:DNA Primers; D051638:Ether-A-Go-Go Potassium Channels / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating; D020033:Protein Isoforms / Q000737:chemistry / Q000502:physiology*; D012559:Schizophrenia / Q000503:physiopathology*
chemical_list: D017931:DNA Primers; D051638:Ether-A-Go-Go Potassium Channels; C486376:KCNH7 protein, human; D020033:Protein Isoforms