Role of glial K+ channels in ontogeny and gliosis: A hypothesis based upon studies on M�ller cells

Bringmann, Andreas; Francke, Mike; Pannicke, Thomas; Biedermann, Bernd; Kodal, Hannes; Faude, Frank; Reichelt, Winfried; Reichenbach, Andreas

doi:10.1002/(sici)1098-1136(20000101)29:1<35::aid-glia4>3.0.co;2-a

Cited by 125 publications

(95 citation statements)

References 68 publications

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“…More detailed studies suggest that K ir channel expression correlates positively with cell differentiation, and K ir activity appears to be absent in proliferating glial cells. This relationship of K ir channel expression and cell differentiation has been demonstrated in astrocytes (MacFarlane and , Schwann cells (Wilson and Chiu, 1990;Konishi, 1994), Müller cells (Bringmann et al, 2000), and oligodendrocytes (Sontheimer et al, 1989;Barres et al, 1990) and thus appears to be a general feature of all glial cells. Intriguingly, changes in the expression and/or activity of K ir channels occur irrespective of how the change in differentiation state is initiated.…”

Section: Introductionmentioning

confidence: 58%

“…We (MacFarlane and Sontheimer, ,2000a and others (Wilson and Chiu, 1990;Konishi, 1994;Bringmann et al, 1999bBringmann et al, ,2000 have previously proposed that K ir channel activity correlates with the differentiation of astrocytes and their exit from the cell cycle. Treatment of immature astrocytes with the differentiation agent retinoic acid leads to a premature differentiation (MacFarlane and Sontheimer, 2000a) and also induces enhanced membrane expression of K ir channels.…”

Section: Discussionmentioning

confidence: 88%

“…Intriguingly, changes in the expression and/or activity of K ir channels occur irrespective of how the change in differentiation state is initiated. For example, in Müller cells of the retina, spontaneous cell maturation causes an increase in K ir channel activity (Bringmann et al, 1999b), but this can be reversed upon cell injury or gliosis, which causes downregulation of channel activity in concert with enhanced glial proliferation (Bringmann et al, 2000). Similarly, acute injury of spinal cord astrocytes leads to a loss of K ir channel activity and more depolarized resting membrane potentials (MacFarlane and .…”

Section: Introductionmentioning

confidence: 99%

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Mislocalization of K_ir channels in malignant glia

Olsen

Sontheimer

2004

Glia

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Inwardly rectifying potassium (K ir ) channels are a prominent feature of mature, postmitotic astrocytes. These channels are believed to set the resting membrane potential near the potassium equilibrium potential (E K ) and are implicated in potassium buffering. A number of previous studies suggest that K ir channel expression is indicative of cell differentiation. We therefore set out to examine K ir channel expression in malignant glia, which are incapable of differentiation. We used two established and widely used glioma cell lines, D54MG (a WHO grade 4 glioma) and STTG-1 (a WHO grade 3 glioma), and compared them to immature and differentiated astrocytes. Both glioma cell lines were characterized by large outward K + currents, depolarized resting membrane potentials (V m )(-38.5 ± 4.2 mV, D54 and -28.1 ± 3.5 mV, STTG1), and relatively high input resistances (R m ) (260.6 ± 64.7 MΩ, D54 and 687.2 ± 160.3 MΩ, STTG1). These features were reminiscent of immature astrocytes, which also displayed large outward K + currents, had a mean V m of -51.1 ± 3.7 and a mean R m value of 627.5 ± 164 MΩ. In contrast, mature astrocytes had a significantly more negative resting membrane potential (-75.2 ± 0.56 mV), and a mean R m of 25.4 ± 7.4 MΩ. Barium (Ba 2+ ) sensitive K ir currents were >20-fold larger in mature astrocytes (4.06 ± 1.1 nS/pF) than in glioma cells (0.169 ± 0.033 nS/pF D54, 0.244 ± 0.04 nS/pF STTG1), which had current densities closer to those of dividing, immature astrocytes (0.474 ± 0.12 nS/pF). Surprisingly, Western blot analysis shows expression of several K ir channel subunits in glioma cells (K ir 2.3, 3.1, and 4.1). However, while in astrocytes these channels localize diffusely throughout the cell, in glioma cells they are found almost exclusively in either the cell nucleus (K ir 2.3 and 4.1) or ER/Golgi (3.1). These data suggest that mislocalization of K ir channel proteins to intracellular compartments is responsible for a lack of appreciable K ir currents in glioma cells.

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Section: Introductionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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Mislocalization of K_ir channels in malignant glia

Olsen

Sontheimer

2004

Glia

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“…Clearly, additional studies are needed to further examine for possible SC cellular dedifferentiation; however, we are limited by the paucity of identified SC-specific markers at present. One potentially promising area will be the exploration of the inwardly rectifying potassium channels (Kir), as a downregulation or inactivation of these channels has been proposed to represent a hallmark of glial cellular dedifferentiation, and to be a precondition for Müller cell proliferation (Bringmann et al 2000).…”

Section: Absence Of Marked Sc Dedifferentationmentioning

confidence: 99%

Supporting Cell Characteristics in Long-deafened Aged Mouse Ears

Oesterle

Campbell

2009

JARO

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Significant sensory hair cell loss leads to irreversible hearing and balance deficits in humans and other mammals. Future therapeutic strategies to repair damaged mammalian auditory epithelium may involve inserting stem cells into the damaged epithelium, inducing non-sensory cells remaining in the epithelium to transdifferentiate into replacement hair cells via gene therapy, or applying growth factors. Little is currently known regarding the status and characteristics of the non-sensory cells that remain in the deafened auditory epithelium, yet this information is integral to the development of therapeutic treatments. A single high-dose injection of the aminoglycoside kanamycin coupled with a single injection of the loop diuretic furosemide was used to kill hair cells in adult mice, and the mice were examined 1 year after the drug insult. Outer hair cells are lost throughout the entire length of the cochlea and less than a third of the inner hair cells remain in the apical turn. Over 20% and 55% of apical organ of Corti support cells and spiral ganglion cells are lost, respectively. We examined the expression of several known support cell markers to investigate for possible support cell dedifferentiation in the damaged ears. The support cell markers investigated included the microtubule protein acetylated tubulin, the transcription factor Sox2, and the Notch signaling ligand Jagged1. Non-sensory epithelial cells remaining in the organ of Corti retain acetylated tubulin, Sox2 and Jagged1 expression, even when the epithelium has a monolayer-like appearance. These results suggest a lack of marked SC dedifferentiation in these aged and badly damaged ears.

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“…However, Kir 4.1 channels are weakly rectifying Kir channels at negative potentials, allowing either 'inward' or 'outward' K + currents, depending on the concentration of extracellular K + . The present study suggests that the acceleration of K + clearance through the Kir 2.1 and Kir 4.1 channels in Müller cells can prevent the effects of neuronal information processing by depolarization caused by glia-derived K + (8,11,12). Adenosine is a natural chemical messenger, which binds to four subtypes (A 1 , A 2A , A 2B and A 3 ) of adenosine receptors (ARs), and regulates the physiological functions of cells.…”

Section: Introductionmentioning

confidence: 85%