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- W2026158637 abstract "Somatodendritic A-type (IA) voltage-gated K+ (KV) channels are key regulators of neuronal excitability, functioning to control action potential waveforms, repetitive firing and the responses to synaptic inputs. Rapidly activating and inactivating somatodendritic IA channels are encoded by KV4 α subunits and accumulating evidence suggests that these channels function as components of macromolecular protein complexes. Mass spectrometry (MS)-based proteomic approaches were developed and exploited here to identify potential components and regulators of native brain KV4.2-encoded IA channel complexes. Using anti-KV4.2 specific antibodies, KV4.2 channel complexes were immunoprecipitated from adult wild type mouse brain. Parallel control experiments were performed on brain samples isolated from (KV4.2-/-) mice harboring a targeted disruption of the KCND2 (KV4.2) locus. Three proteomic strategies were employed: an in-gel approach, coupled to one-dimensional liquid chromatography-tandem MS (1D-LC-MS/MS), and two in-solution approaches, followed by 1D- or 2D-LC-MS/MS. The targeted in-gel 1D-LC-MS/MS analyses demonstrated the presence of the Kv4 α subunits (KV4.2, KV4.3 and KV4.1) and the KV4 accessory, KChIP (KChIP1-4) and DPP (DPP6 and 10), proteins in native brain KV4.2 channel complexes. The more comprehensive, in-solution approach, coupled to 2D-LC-MS/MS, also called Multidimensional Protein Identification Technology (MudPIT), revealed that additional regulatory proteins, including the Kv channel accessory subunit KVβ1, are also components of native brain KV4.2 channel complexes. Additional biochemical and functional approaches will be required to elucidate the physiological roles of these newly identified KV4 interacting proteins." @default.
- W2026158637 created "2016-06-24" @default.
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- W2026158637 date "2009-07-31" @default.
- W2026158637 modified "2023-10-16" @default.
- W2026158637 title "Proteomic analyses of native brain K<sub>V</sub>4.2 channel complexes" @default.
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- W2026158637 doi "https://doi.org/10.4161/chan.3.4.9553" @default.
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