TNFα induces a protein kinase C-dependent reduction in astroglial K+ conductance

Köller, Hubertus; Allert, Niels; Oel, Dierk; Stoll, Guido; Siebler, Mario

doi:10.1097/00001756-199805110-00023

Cited by 46 publications

(34 citation statements)

References 13 publications

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“…However, we failed to observe any alteration in the expression of laminin in immunohistochemically stained slices of 2-or 7-day postischemic rat retinae if compared with controls (Pannicke et al, 2004). In cultured astrocytes, addition of tumor necrosis factor-␣ (TNF-␣) to the culture medium resulted in a reduction of Kir currents (Köller et al, 1998). The present results suggest that hitherto unknown stimuli, which occur in ischemia-reperfusion, but not in certain other retinal degenerations of the rat, may lead to the observed alteration of K ϩ channel expression.…”

Section: Discussionmentioning

confidence: 76%

Altered membrane physiology in Müller glial cells after transient ischemia of the rat retina

Pannicke

Uckermann

Iandiev

et al. 2004

Glia

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Inwardly rectifying K+ (Kir) channels have been implicated in the mediation of retinal K+ homeostasis by Muller glial cells. To assess possible involvement of altered glial K+ channel expression in ischemia-reperfusion injury, transient retinal ischemia was induced in rat eyes. Acutely isolated Muller cells from postischemic retinae displayed a fast downregulation of their Kir currents, which began within 1 day and reached a maximum at 3 days of reperfusion, with a peak decrease to 20% as compared with control. This strong decrease of Kir currents was accompanied by an increase of the incidence of cells which displayed depolarization-evoked fast transient (A-type) K+ currents. While no cell from untreated control rats expressed A-type K+ currents, all cells investigated from 3- and 7-day postischemic retinae displayed such currents. An increased incidence of cells displaying fast transient Na+ currents was observed at 7 days after ischemia. These results suggest a role of altered glial Kir channel expression in postischemic neuronal degeneration via disturbance of retinal K+ siphoning.

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Section: Discussionmentioning

confidence: 76%

Altered membrane physiology in Müller glial cells after transient ischemia of the rat retina

Pannicke

Uckermann

Iandiev

et al. 2004

Glia

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“…Moreover, transcription has previously been linked to cell depolarization (54). It appears from the current experiments that membrane depolarization of reactive astrocytes is an early signaling event following activation by TGF-␤ 1 and possibly by other cytokines as well (40). Cytokine-mediated regulation of membrane potential represents a new, potentially important aspect in understanding the function of reactive astrocytes.…”

Section: Discussionmentioning

confidence: 82%

Transforming Growth Factor-β1 Regulates Kir2.3 Inward Rectifier K+ Channels via Phospholipase C and Protein Kinase C-δ in Reactive Astrocytes from Adult Rat Brain

Perillan¹,

Chen²,

Potts³

et al. 2002

Journal of Biological Chemistry

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The multifunctional cytokine, transforming growth factor ␤ 1 (TGF-␤ 1 ), exerts complex effects on astrocytes with early signaling events being less well characterized than transcriptional mechanisms. We examined the effect of TGF-␤ 1 on the 14-pS Kir2.3 inward rectifier K ؉ channel in rat primary cultured reactive astrocytes. Immunofluorescence study showed that cells co-expressed TGF-␤ 1 receptors 1 and 2, Kir2.3, and glial fibrillary acidic protein (GFAP). Patch clamp study showed that TGF-␤ 1 (0.1-100 ng/ml) caused a rapid (<5 min) depolarization because of dose-dependent down-regulation of Kir2.3 channels, which was mimicked by the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (10 -500 nM) and which was inhibited by the PKC inhibitor calphostin C (100 nM), by PKC desensitization produced by 3 h of exposure to phorbol 12-myristate 13-acetate (100 nM), and by the PKC-␦ isoform-specific inhibitor rottlerin (50 M). Immunoblot analysis and confocal imaging showed that TGF-␤ 1 caused PKC-␦ translocation to membrane, and co-immunoprecipitation experiments showed that TGF-␤ 1 enhanced association between Kir2.3 and PKC-␦. Additional electrophysiological experiments showed that Kir2.3 channel down-regulation was blocked by the phospholipase C inhibitors, neomycin (100 M) and D609 (200 M). Given

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“…Second, the observations reported here may not apply to all mammalian tissues. In particular, in astrocytes, TNF has been shown to inhibit rather than activate K ϩ currents (34). Thus, the results reported in the present study must be extrapolated with care.…”

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confidence: 74%

Activation of Potassium and Chloride Channels by Tumor Necrosis Factor α

Nietsch

Roe

Fiekers

et al. 2000

Journal of Biological Chemistry

107

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Despite abundant evidence for changes in mitochondrial membrane permeability in tumor necrosis factor (TNF)-mediated cell death, the role of plasma membrane ion channels in this process remains unclear. These studies examine the influence of TNF on ion channel opening and death in a model rat liver cell line (HTC). TNF (25 ng/ml) elicited a 2-and 5-fold increase in K ؉ and Cl ؊ currents, respectively, in HTC cells. These increases occurred within 5-10 min after TNF exposure and were inhibited either by K ؉ or Cl ؊ substitution or by K ؉ channel blockers (Ba 2؉ , quinine, 0.1 mM each) or Cl ؊ channel blockers (10 M 5-nitro-2-(3-phenylpropylamino)benzoic acid and 0.1 mM N-phenylanthranilic acid), respectively. TNF-mediated increases in K ؉ and Cl ؊ currents were each inhibited by intracellular Ca 2؉ chelation (5 mM EGTA), ATP depletion (4 units/ml apyrase), and the protein kinase C (PKC) inhibitors chelerythrine (10 M) or PKC 19 -36 peptide (1 M). In contrast, currents were not attenuated by the calmodulin kinase II 281-309 peptide (10 M), an inhibitor of calmodulin kinase II. In the presence of actinomycin D (1 M), each of the above ion channel blockers significantly delayed the progression to TNF-mediated cell death. Collectively, these data suggest that activation of K ؉ and Cl ؊ channels is an early response to TNF signaling and that channel opening is Ca 2؉ -and PKC-dependent. Our findings further suggest that K ؉ and Cl ؊ channels participate in pathways leading to TNF-mediated cell death and thus represent potential therapeutic targets to attenuate liver injury from TNF.

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TNFα induces a protein kinase C-dependent reduction in astroglial K+ conductance

Cited by 46 publications

References 13 publications

Altered membrane physiology in Müller glial cells after transient ischemia of the rat retina

Altered membrane physiology in Müller glial cells after transient ischemia of the rat retina

Transforming Growth Factor-β1 Regulates Kir2.3 Inward Rectifier K+ Channels via Phospholipase C and Protein Kinase C-δ in Reactive Astrocytes from Adult Rat Brain

Activation of Potassium and Chloride Channels by Tumor Necrosis Factor α

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