Referenced in: none

Automatically associated channels: Kv1.3

Title: Activated T-cells inhibit neurogenesis by releasing granzyme B: rescue by Kv1.3 blockers.

Authors: Tongguang Wang, Myoung-Hwa Lee, Tory Johnson, Rameeza Allie, Lina Hu, Peter A Calabresi, Avindra Nath

Journal, date & volume: J. Neurosci., 2010 Apr 7 , 30, 5020-7

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20371822

Abstract
There is a great need for pharmacological approaches to enhance neural progenitor cell (NPC) function particularly in neuroinflammatory diseases with failed neuroregeneration. In diseases such as multiple sclerosis and stroke, T-cell infiltration occurs in periventricular zones where NPCs are located and is associated with irreversible neuronal loss. We studied the effect of T-cell activation on NPC functions. NPC proliferation and neuronal differentiation were impaired by granzyme B (GrB) released by the T-cells. GrB mediated its effects by the activation of a Gi-protein-coupled receptor leading to decreased intracellular levels of cAMP and subsequent expression of the voltage-dependent potassium channel, Kv1.3. Importantly, blocking channel activity with margatoxin or blocking its expression reversed the inhibitory effects of GrB on NPCs. We have thus identified a novel pathway in neurogenesis. The increased expression of Kv1.3 in pathological conditions makes it a novel target for promoting neurorestoration.