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PLoS One. 2009 Aug 26;4(8):e6770. doi: 10.1371/journal.pone.0006770.

Predominant functional expression of Kv1.3 by activated microglia of the hippocampus after Status epilepticus.

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  • 1Institut National de la Santé et de la Recherche Médicale, Unité 603, Paris, France.

Abstract

BACKGROUND:

Growing evidence indicates that the functional state of microglial cells differs according to the pathological conditions that trigger their activation. In particular, activated microglial cells can express sets of Kv subunits which sustain delayed rectifying potassium currents (Kdr) and modulate differently microglia proliferation and ability to release mediators. We recently reported that hippocampal microglia is in a particular activation state after a status epilepticus (SE) and the present study aimed at identifying which of the Kv channels are functionally expressed by microglia in this model.

METHODOLOGY/PRINCIPAL FINDINGS:

SE was induced by systemic injection of kainate in CX3CR1(eGFP/+) mice and whole cell recordings of fluorescent microglia were performed in acute hippocampal slices prepared 48 h after SE. Microglia expressed Kdr currents which were characterized by a potential of half-maximal activation near -25 mV, prominent steady-state and cumulative inactivations. Kdr currents were almost abolished by the broad spectrum antagonist 4-Aminopyridine (1 mM). In contrast, tetraethylammonium (TEA) at a concentration of 1 mM, known to block Kv3.1, Kv1.1 and 1.2 subunits, only weakly reduced Kdr currents. However, at a concentration of 5 mM which should also affect Kv1.3 and 1.6, TEA inhibited about 30% of the Kdr conductance. Alpha-dendrotoxin, which selectively inhibits Kv1.1, 1.2 and 1.6, reduced only weakly Kdr currents, indicating that channels formed by homomeric assemblies of these subunits are not important contributors of Kdr currents. Finally, agitoxin-2 and margatoxin strongly inhibited the current.

CONCLUSIONS/SIGNIFICANCE:

These results indicate that Kv1.3 containing channels predominantly determined Kdr currents in activated microglia after SE.

PMID:
19707551
[PubMed - indexed for MEDLINE]
PMCID:
PMC2727945
Free PMC Article

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