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Disruption of K V 2.1 somato-dendritic clusters prevents the apoptogenic increase of potassium currents.
- Source :
-
Neuroscience [Neuroscience] 2017 Jun 23; Vol. 354, pp. 158-167. Date of Electronic Publication: 2017 Apr 28. - Publication Year :
- 2017
-
Abstract
- As the predominant mediator of the delayed rectifier current, K <subscript>V</subscript> 2.1 is an important regulator of neuronal excitability. K <subscript>V</subscript> 2.1, however, also plays a well-established role in apoptotic cell death. Apoptogenic stimuli induce syntaxin-dependent trafficking of K <subscript>V</subscript> 2.1, resulting in an augmented delayed rectifier current that acts as a conduit for K <superscript>+</superscript> efflux required for pro-apoptotic protease/nuclease activation. Recent evidence suggests that K <subscript>V</subscript> 2.1 somato-dendritic clusters regulate the formation of endoplasmic reticulum-plasma membrane junctions that function as scaffolding sites for plasma membrane trafficking of ion channels, including K <subscript>V</subscript> 2.1. However, it is unknown whether K <subscript>V</subscript> 2.1 somato-dendritic clusters are required for apoptogenic trafficking of K <subscript>V</subscript> 2.1. By overexpression of a protein derived from the C-terminus of the cognate channel K <subscript>V</subscript> 2.2 (K <subscript>V</subscript> 2.2CT), we induced calcineurin-independent disruption of K <subscript>V</subscript> 2.1 somato-dendritic clusters in rat cortical neurons, without altering the electrophysiological properties of the channel. We observed that K <subscript>V</subscript> 2.2CT-expressing neurons are less susceptible to oxidative stress-induced cell death. Critically, expression of K <subscript>V</subscript> 2.2CT effectively blocked the increased current density of the delayed rectifier current associated with oxidative injury, supporting a vital role of K <subscript>V</subscript> 2.1-somato-dendritic clusters in apoptogenic increases in K <subscript>V</subscript> 2.1-mediated currents.<br /> (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Apoptosis physiology
Cells, Cultured
Cerebral Cortex cytology
Cholinesterase Inhibitors pharmacology
Cricetulus
Dendrites genetics
Embryo, Mammalian
Enzyme Inhibitors pharmacology
Ethylenediamines pharmacology
Female
Immunosuppressive Agents pharmacology
Membrane Potentials drug effects
Membrane Potentials genetics
Microglia metabolism
Neurons physiology
Pregnancy
Pyridines toxicity
Rats
Shab Potassium Channels genetics
Tacrolimus analogs & derivatives
Tacrolimus pharmacology
Apoptosis genetics
Dendrites metabolism
Neurons cytology
Shab Potassium Channels metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7544
- Volume :
- 354
- Database :
- MEDLINE
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 28461216
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2017.04.034