Article

Analysis of Astroglial K+ Channel Expression in the Developing Hippocampus Reveals a Predominant Role of the Kir4.1 Subunit

Institute of Cellular Neurosciences, University of Bonn, D-53105 Bonn, Germany.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.75). 07/2009; 29(23):7474-88. DOI: 10.1523/JNEUROSCI.3790-08.2009
Source: PubMed

ABSTRACT Astrocytes in different brain regions display variable functional properties. In the hippocampus, astrocytes predominantly express time- and voltage-independent currents, but the underlying ion channels are not well defined. This ignorance is partly attributable to abundant intercellular coupling of these cells through gap junctions, impeding quantitative analyses of intrinsic membrane properties. Moreover, distinct types of cells with astroglial properties coexist in a given brain area, a finding that confused previous analyses. In the present study, we investigated expression of inwardly rectifying (Kir) and two-pore-domain (K2P) K+ channels in astrocytes, which are thought to be instrumental in the regulation of K+ homeostasis. Freshly isolated astrocytes were used to improve space-clamp conditions and allow for quantitative assessment of functional parameters. Patch-clamp recordings were combined with immunocytochemistry, Western blot analysis, and semiquantitative transcript analysis. Comparative measurements were performed in different CA1 subregions of astrocyte-targeted transgenic mice. While confirming weak Ba2+ sensitivity in situ, our data demonstrate that in freshly isolated astrocytes, the main proportion of membrane currents is sensitive to micromolar Ba2+ concentrations. Upregulation of Kir4.1 transcripts and protein during the first 10 postnatal days was accompanied by a fourfold increase in astrocyte inward current density. Hippocampal astrocytes from Kir4.1-/- mice lacked Ba2+-sensitive currents. In addition, we report functional expression of K2P channels of the TREK subfamily (TREK1, TREK2), which mediate astroglial outward currents. Together, our findings demonstrate that Kir4.1 constitutes the pivotal K+ channel subunit and that superposition of currents through Kir4.1 and TREK channels underlies the "passive" current pattern of hippocampal astrocytes.

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    • "Various attempts to correlate the biochemical and functional properties of discrete astrocytic population were then pursued by using diverse approaches. Differences in the current profile of distinct astrocyte subsets were ascribed to the heterogeneous expression of ion channels, including inward rectifying K + (Kir) channels (Butt and Kalsi, 2006; Kofuji et al., 2000; Neusch et al., 2006; Olsen et al., 2007; Seifert et al., 2009). For instance, the K + channel subunit Kir4.1 was described to be abundantly expressed in astrocytes of the spinal cord ventral horns when compared to those of the dorsal horns. "
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    • "The passive conductance implies an abundant and combined expression of multiple leak-type K ϩ channels , such as inwardly rectifying K ir 4.1, two-pore domain K ϩ channels, and Ca 2ϩ -activated K ϩ channels (Chever et al. 2010; Chu et al. 2010; Djukic et al. 2007; Hwang et al. 2014; Kucheryavykh et al. 2007; Longden et al. 2011; Olsen and Sontheimer 2008; Seifert et al. 2009; Skatchkov et al. 2006; Tong et al. 2014). The extremely low R m shown in single astrocytes also suggests that the transmembrane K "
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    • "ed in water balance and ( functionally related ) potassium buffering . Aquaporin 4 appears after PND20 and its levels increase afterwards , according to single - cell gene expression data ( Rusnakova et al . , 2013 ) . The major potassium channel Kir4 . 1 is downregulated to its stable level in the hippocampus within the first ten postnatal days ( Seifert et al . , 2009 ) . In contrast to most astrocytic receptors , the lev - els of GFAP as well as of the calcium binding protein s100b increase during aging ( Nichols , 1999 ; Sheng et al . , 1996 ) . In accord with these observations , a global increase in GFAP expression in the aged brain is detectable , suggesting an increased number of astrocytes in "
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