• Jason A Justice, Anthony J Schulien, Kai He, Karen A Hartnett, Elias Aizenman, and Niyathi H Shah.
• Department of Neurobiology and Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. Electronic address: jjustice@pitt.edu.
• Neuroscience. 2017 Jun 23; 354: 158-167.

AbstractAs the predominant mediator of the delayed rectifier current, KV2.1 is an important regulator of neuronal excitability. KV2.1, however, also plays a well-established role in apoptotic cell death. Apoptogenic stimuli induce syntaxin-dependent trafficking of KV2.1, resulting in an augmented delayed rectifier current that acts as a conduit for K+ efflux required for pro-apoptotic protease/nuclease activation. Recent evidence suggests that KV2.1 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 KV2.1. However, it is unknown whether KV2.1 somato-dendritic clusters are required for apoptogenic trafficking of KV2.1. By overexpression of a protein derived from the C-terminus of the cognate channel KV2.2 (KV2.2CT), we induced calcineurin-independent disruption of KV2.1 somato-dendritic clusters in rat cortical neurons, without altering the electrophysiological properties of the channel. We observed that KV2.2CT-expressing neurons are less susceptible to oxidative stress-induced cell death. Critically, expression of KV2.2CT effectively blocked the increased current density of the delayed rectifier current associated with oxidative injury, supporting a vital role of KV2.1-somato-dendritic clusters in apoptogenic increases in KV2.1-mediated currents.Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

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