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The Journal of Neuroscience, June 10, 2009, 29(23):7474-7488; doi:10.1523/JNEUROSCI.3790-08.2009

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

Gerald Seifert,¹ Kerstin Hüttmann,¹ Devin K. Binder,² Christian Hartmann,¹ Alexandra Wyczynski,¹ Clemens Neusch,³ and Christian Steinhäuser¹

¹Institute of Cellular Neurosciences, University of Bonn, D-53105 Bonn, Germany, ²Department of Neurological Surgery, University of California, Irvine, Irvine, California 92868-3298, and ³Department of Neurology, University of Göttingen, D-37099 Göttingen, Germany

Correspondence should be addressed to Dr. Christian Steinhäuser, Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany. Email: christian.steinhaeuser{at}ukb.uni-bonn.de

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 (K_2P) 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 K_2P 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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Received Aug. 11, 2008; revised April 28, 2009; accepted May 5, 2009.

Correspondence should be addressed to Dr. Christian Steinhäuser, Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany. Email: christian.steinhaeuser{at}ukb.uni-bonn.de

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