Channelpedia

PubMed 17868321


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kv1.3



Title: Minocycline decreases in vitro microglial motility, beta1-integrin, and Kv1.3 channel expression.

Authors: Nancy Nutile-McMenemy, Arye Elfenbein, Joyce A Deleo

Journal, date & volume: J. Neurochem., 2007 Dec , 103, 2035-46

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17868321


Abstract
Minocycline is a semisynthetic, tetracycline derivative that exerts anti-inflammatory and neuroprotective effects unrelated to its anti-microbial action. We have previously shown that minocycline prevented peripheral nerve injury-induced mechanical allodynia. Minocycline's mechanisms of action as a neuroprotective and anti-allodynic agent are unknown. In response to injury, microglia become activated, proliferate, and migrate. Resting microglia express voltage-dependent inward K(+) currents and blocking Kv1.3 channels has been shown to inhibit microglial-mediated neuronal death. We investigated the effect of minocycline on the expression of Kv channels, cell motility, and beta-integrin expression using primary rat cortical microglia, transwell assays, and by flow cytometry. Minocycline significantly reduced microglial migration to cellular debris, astrocyte-conditioned medium, ADP, and algesic mediators and significantly reduced the expression of CD29 (beta(1)-integrin) but not CD18 (beta(2)-integrin). Minocycline reduced the effect of extracellular potassium and later decreased microglial Kv1.3 expression. In summary, we uncovered a novel effect of minocycline that demonstrates this agent decreases microglial beta(1)-integrin expression, which leads to inhibition of motility. We propose an in vivo model whereby reduced microglial trafficking to injured neurons following nerve injury decreases the release of proinflammatory mediators into the synaptic milieu, preventing neuronal sensitization, the pathological correlate to chronic pain.