At present, the role of microglial K
+ currents in physiological conditions is still poorly understood [
47]. It is known that K
ir channels are specifically responsible for stabilization of the resting membrane potential and subsequent Ca
2+ signaling [
148,
149]. We reported similar amplitude of K
ir currents in DH and VH microglia and, in line with previous studies, the membrane potential values for microglial cells were comparable. By contrast, we found that microglia differ in their ability to produce K
or currents at the two hippocampal poles, being this current increased in VH compared to DH. Interestingly, this difference is associated with variations in
Il-1β,
Tnf-α, and
Il-6 expression levels in CD11b
+ cells. These cytokines have been shown to be regulated by K
+ channel, among CD11b
+ cells. Specifically, K
v1.3 seems to be a key factor in regulating the release of several cytokines upon stimuli and its knockout or deletion results in a reduction of IL-1β, TNF-α, and IL-6 release mediated by LPS [
148,
150‐
152]. In addition, K
v1.3 mRNA and channel expression were augmented by a pro-inflammatory stimuli such as LPS, IFN-γ, or TNF-α treatment [
142,
145,
153,
154] or an anti-inflammatory one (IL-4) indicating that the elevated expression of this channel is not a reliable marker of exclusively pro-inflammatory microglial state [
154]. Overall, these studies support the notion that the K
v1.3 channels play a crucial role in controlling microglial release of cytokines. We speculate that in steady-state conditions, differences in this K
+ current could be related to changes in
Il-1β,
Tnf-α, and
Il-6 expression. Although the percentage of microglia cells expressing K
or at both poles is around 50%, we can speculate that the different microglial K
or currents amplitude in VH versus DH could be linked to a specific level of cytokines released by microglia, that in turn could affect plasticity in a region-dependent manner. Further analyses are needed to better elucidate the mechanisms underlying this modulation and the functional implication of microglial differences in the K
or current at the two poles. Interestingly, the occurrence of the K
or current, which peaks during the second and third postnatal weeks, is reduced in
Cx3cr1−/− mice [
155]. Here we observed that, in the Cx3cr1
+/GFP mice, the average amplitude of microglial outward K
+ currents is increased in the VH, where
Cx3cr1 mRNA levels are higher compared to the DH, supporting a positive correlation between the CX3CR1 and K
+ current occurrence. It must be stressed out that Cx3cr1
+/GFP mice
, extensively used to characterize microglia features, cannot be considered as wild-type mice, as they show an intermediate phenotype between wild-type and Cx3cr1
−/− in different parameters such as LTP basal amplitude [
37]. Therefore, it is possible that using Cx3cr1
+/GFP mice we underestimate the differences in K
+ currents, and further analysis in CTRL mice will be necessary to better elucidate microglia functional state in DH and VH.