Calcium influx mediated by the inwardly rectifying K+ channel Kir4.1 (KCNJ10) at low external K+ concentration

Härtel, Kai; Singaravelu, Karthika; Kaiser, Melanie; Neusch, Clemens; Hülsmann, Swen; Deitmer, Joachim W.

doi:10.1016/j.ceca.2006.12.004

Cited by 42 publications

(40 citation statements)

References 34 publications

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“…Over activation of NMDA receptors has been shown to lead to decreased Kir4.1 expression (ObaraMichlewska et al, 2015), suggesting a possible feedback loop between Kir4.1 and the consequences of Glt1 loss in HD. A critical role for Kir4.1 in these phenomena is supported by past cell biological studies (Härtel et al, 2007;Kucheryavykh et al, 2007) and suggests that correcting Kir4.1-dependent homeostatic functions in astrocytes has downstream beneficial effects via Glt1 and Ca 2ϩ . Disentangling cause and effect and revealing potential convergent molecular mechanisms among Kir4.1, Glt1, and Ca 2ϩ will require further detailed work, but could include gene and/or protein regulation, the influence of electrochemical driving force, altered ion selectivity (Härtel et al, 2007), or possibly all four.…”

Section: Discussionmentioning

confidence: 61%

“…A critical role for Kir4.1 in these phenomena is supported by past cell biological studies (Härtel et al, 2007;Kucheryavykh et al, 2007) and suggests that correcting Kir4.1-dependent homeostatic functions in astrocytes has downstream beneficial effects via Glt1 and Ca 2ϩ . Disentangling cause and effect and revealing potential convergent molecular mechanisms among Kir4.1, Glt1, and Ca 2ϩ will require further detailed work, but could include gene and/or protein regulation, the influence of electrochemical driving force, altered ion selectivity (Härtel et al, 2007), or possibly all four. Moreover, the available data do not suggest a simple all-encompassing, circuit-based mechanism for how astrocytes cause or contribute to HD symptoms, largely because there is no accepted neural circuit based model for HD per se (Waldvogel et al, 2015;Plotkin and Surmeier, 2015).…”

Section: Discussionmentioning

confidence: 61%

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Dysfunctional Calcium and Glutamate Signaling in Striatal Astrocytes from Huntington's Disease Model Mice

et al. 2016

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 61%

Dysfunctional Calcium and Glutamate Signaling in Striatal Astrocytes from Huntington's Disease Model Mice

et al. 2016

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“…We hypothesized that the application of Ba 2ϩ may alter the membrane potential of EPCs. Many papers have reported that the blockage of Kir depolarizes the membrane potential and induces a change in calcium concentration (10). Before conducting the experiment, we optimized the experimental conditions by changing the membrane potential.…”

Section: Characterization Of Human Umbilical Cord Blood-derivedmentioning

confidence: 99%

Endothelial progenitor cells functionally express inward rectifier potassium channels

Jang

Park

Hur

et al. 2011

American Journal of Physiology-Cell Physiology

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Since the first isolation of endothelial progenitor cells (EPCs) from human peripheral blood in 1997, many researchers have conducted studies to understand the characteristics and therapeutic effects of EPCs in vascular disease models. Nevertheless, the electrophysiological properties of EPCs have yet to be clearly elucidated. The inward rectifier potassium channel (Kir) performs a major role in controlling the membrane potential and cellular events. Here, via the whole cell patch-clamp technique, we found inwardly rectifying currents in EPCs and that these currents were inhibited by Ba(2+) (100 μM) and Cs(+) (1 mM), known as Kir blockers, in a dose-dependent manner (Ba(2+), 91.2 ± 1.4% at -140 mV and Cs(+), 76.1 ± 6.9% at -140 mV, respectively). Next, using DiBAC(3), a fluorescence indicator of membrane potential, we verified that Ba(2+) induced an increase of fluorescence in EPCs (10 μM, 123 ± 2.8%), implying the depolarization of EPCs. At the mRNA and protein levels, we confirmed the existence of several Kir subtypes, including Kir2.x, 3.x, 4.x, and 6.x. In a functional experiment, we observed that, in the presence of Ba(2+), the number of tubes on Matrigel formed by EPCs was dose-dependently reduced (10 μM, 62.3 ± 6.5%). In addition, the proliferation of EPCs was increased in a dose-dependent fashion (10 μM, 157.9 ± 17.4%), and specific inhibition of Kir2.1 by small interfering RNA also increased the proliferation of EPCs (116.2 ± 2.5%). Our results demonstrate that EPCs express several types of Kir which may modulate the endothelial function and proliferation of EPCs.

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“…extracellular K ϩ concentrations. Thus, under conditions of local K ϩ undershoot attributable to enhanced Na ϩ /K ϩ ATPase activity, Kir4.1 channels potentially trigger Ca 2ϩ oscillations and gliotransmitter release, which might exacerbate pathological conditions (Dallwig et al, 2000;Hartel et al, 2007).…”

Section: Pathological Impact Of Kir41 Regulation In Astrocytesmentioning

confidence: 99%

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

Seifert¹,

Hüttmann²,

Binder³

et al. 2009

Journal of Neuroscience

200

226

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Astrocytes in different brain regions display variable functional properties. In the hippocampus, astrocytes predominantly express timeand 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 ϩ channels in astrocytes, which are thought to be instrumental in the regulation of K ϩ 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 Ba 2ϩ sensitivity in situ, our data demonstrate that in freshly isolated astrocytes, the main proportion of membrane currents is sensitive to micromolar Ba 2ϩ 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 Kir4.1Ϫ/Ϫ mice lacked Ba 2ϩ -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 ϩ 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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Calcium influx mediated by the inwardly rectifying K+ channel Kir4.1 (KCNJ10) at low external K+ concentration

Cited by 42 publications

References 34 publications

Dysfunctional Calcium and Glutamate Signaling in Striatal Astrocytes from Huntington's Disease Model Mice

Dysfunctional Calcium and Glutamate Signaling in Striatal Astrocytes from Huntington's Disease Model Mice

Endothelial progenitor cells functionally express inward rectifier potassium channels

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

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