Abstract
BackgroundGrowing 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 FindingsSE was induced by systemic injection of kainate in CX3CR1eGFP/+ 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/SignificanceThese results indicate that Kv1.3 containing channels predominantly determined Kdr currents in activated microglia after SE.
Highlights
Recent experimental evidence has considerably expanded our knowledge of the biology and functions of microglia, the brain resident macrophages
The activation state developed by microglia in response to various stimuli is not unique: different stimuli and different contexts lead microglia to develop different functional states which correspond to a diversity of functions of microglia underlying their deleterious or beneficial effects on neuronal survival and function
Whole-cell recordings performed in acute hippocampal slices showed that the current-voltage relationship of microglia recorded in the stratum radiatum of the CA1 region of control mice was almost linear between membrane potentials of 2140 to +40 mV (Fig. 1B)
Summary
Recent experimental evidence has considerably expanded our knowledge of the biology and functions of microglia, the brain resident macrophages. As far as Kdr channels are concerned, several subunits have been identified in microglia and seem to control different functional aspects of its activation. Both Kv1.3 and Kv1.5 channels modulate the proliferation of activated microglial cells [13,15]. A role for Kv1.5 channels in controlling the LPS-induced release of nitric oxide by microglia has been proposed [13], a calcium-activated potassium channel, KCa3.1, modulates this release [17]. 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
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