Effects of barium, furosemide, ouabaine and 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS) on ionophoretically-induced changes in extracellular potassium concentration in hippocampal slices from rats and from patients with epilepsy

Jauch, Regina; Windmüller, Olaf; Lehmann, Thomas‐Nicolas; Heinemann, Uwe; Gabriel, Siegrun

doi:10.1016/s0006-8993(01)03254-1

Cited by 63 publications

(52 citation statements)

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“…In line with this assumption was also the observation of impaired K 1 buffering and prolonged seizure duration in AQP4 knockout mice (Binder et al, 2006) although spatial K 1 redistribution was more efficient in these mice, probably due to enhanced astrocyte gap junction coupling and volume regulation (Benfenati et al, 2011;Strohschein et al, 2011). However, more recent data from astrocytes and retinal M€ uller cells suggested that Kir4.1 channel function is independent of AQP4 expression (Ruiz-Ederra et al, 2007;Zhang and Verkman, 2008 , this finding suggested impaired function of these channels in the sclerotic tissue (Jauch et al, 2002;Kivi et al, 2000). The hypothesis could be confirmed with patch-clamp analyses demonstrating downregulation of Kir currents in the CA1 region of HS patients (Bordey and Sontheimer, 1998;Hinterkeuser et al, 2000).…”

Section: Impact Of Inwardly Rectifying Kmentioning

confidence: 78%

Astrocyte dysfunction in temporal lobe epilepsy: K⁺ channels and gap junction coupling

Steinhäuser

Seifert

Bedner

2012

Glia

173

172

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Astrocytes are endowed with the machinery to sense and respond to neuronal activity. Recent work has demonstrated that astrocytes play important physiological roles in the CNS, e.g., they synchronize action potential firing, ensure ion homeostasis, transmitter clearance and glucose metabolism, and regulate the vascular tone. Astrocytes are abundantly coupled through gap junctions, which is a prerequisite to redistribute elevated K 1 from sites of excessive neuronal activity to sites of lower extracellular K 1 concentration. Recent studies identified dysfunctional astrocytes as crucial players in epilepsy. Investigation of specimens from patients with pharmacoresistant temporal lobe epilepsy and epilepsy models revealed alterations in expression, localization, and function of astroglial inwardly rectifying K 1 (Kir) channels, particularly Kir4.1, which is suspected to entail impaired K 1 buffering. Gap junctions in astrocytes appear to play a dual role: on the one hand they counteract the generation of hyperactivity by facilitating clearance of elevated extracellular K 1 levels while in contrast, they constitute a pathway for energetic substrate delivery to fuel neuronal (hyper)activity. Recent work suggests that astrocyte dysfunction is causative of the generation or spread of seizure activity. Thus, astrocytes should be considered as promising targets for alternative antiepileptic therapies. V V C 2012 Wiley Periodicals, Inc.

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Section: Impact Of Inwardly Rectifying Kmentioning

confidence: 78%

Astrocyte dysfunction in temporal lobe epilepsy: K⁺ channels and gap junction coupling

Steinhäuser

Seifert

Bedner

2012

Glia

173

172

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“…5C,D). Slow buffering processes mainly represent net uptake of K ϩ via the neuronal Na ϩ /K ϩ ATPase because they are strophantidine sensitive (Ransom et al, 2000) and because the undershoot (Heinemann and Lux, 1975) is not seen when neuronal activity is blocked and K ϩ is applied iontophoretically (Jauch et al, 2002). Indeed, amplitudes of undershoots in dko mice were unchanged (see Results).…”

Section: Astrocytic Kmentioning

confidence: 90%

The Impact of Astrocytic Gap Junctional Coupling on Potassium Buffering in the Hippocampus

Wallraff¹,

Köhling²,

Heinemann³

et al. 2006

J. Neurosci.

517

570

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Astrocytic gap junctions have been suggested to contribute to spatial buffering of potassium in the brain. Direct evidence has been difficult to gather because of the lack of astrocyte-specific gap junction blockers. We obtained mice with coupling-deficient astrocytes by crossing conditional connexin43-deficient mice with connexin30 Ϫ/Ϫ mice. Similar to wild-type astrocytes, genetically uncoupled hippocampal astrocytes displayed negative resting membrane potentials, time-and voltage-independent whole-cell currents, and typical astrocyte morphologies. Astrocyte densities were also unchanged. Using potassium-selective microelectrodes, we assessed changes in potassium buffering in hippocampal slices of mice with coupling-deficient astrocytes. We demonstrate that astrocytic gap junctions accelerate potassium clearance, limit potassium accumulation during synchronized neuronal firing, and aid in radial potassium relocation in the stratum lacunosum moleculare. Furthermore, slices of mice with coupling-deficient astrocytes displayed a reduced threshold for the generation of epileptiform events. However, it was evident that radial relocation of potassium in the stratum radiatum was not dependent on gap junctional coupling. We suggest that the perpendicular array of individual astrocytes in the stratum radiatum makes these cells ideally suited for spatial buffering of potassium released by pyramidal cells, independent of gap junctions. In general, a surprisingly large capacity for K ϩ clearance was conserved in mice with coupling-deficient astrocytes, indicating that gap junctiondependent processes only partially account for K ϩ buffering in the hippocampus.

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“…Examination of the membranes of glial cells obtained from patients with intractable epilepsies sometimes demonstrates a near-complete lack of Kir conductance (58), reduction of the inward rectification (267), and an impaired ability for K ϩ clearance (200,331). Two early studies reported that mutations of the Kir4.1 gene might be involved in epilepsy and seizure.…”

Section: Diseasesmentioning

confidence: 99%

Inwardly Rectifying Potassium Channels: Their Structure, Function, and Physiological Roles

Hibino

Inanobe

Furutani

et al. 2010

Physiological Reviews

1,296

1,496

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Inwardly rectifying K+(Kir) channels allow K+to move more easily into rather than out of the cell. They have diverse physiological functions depending on their type and their location. There are seven Kir channel subfamilies that can be classified into four functional groups: classical Kir channels (Kir2.x) are constitutively active, G protein-gated Kir channels (Kir3.x) are regulated by G protein-coupled receptors, ATP-sensitive K+channels (Kir6.x) are tightly linked to cellular metabolism, and K+transport channels (Kir1.x, Kir4.x, Kir5.x, and Kir7.x). Inward rectification results from pore block by intracellular substances such as Mg2+and polyamines. Kir channel activity can be modulated by ions, phospholipids, and binding proteins. The basic building block of a Kir channel is made up of two transmembrane helices with cytoplasmic NH2and COOH termini and an extracellular loop which folds back to form the pore-lining ion selectivity filter. In vivo, functional Kir channels are composed of four such subunits which are either homo- or heterotetramers. Gene targeting and genetic analysis have linked Kir channel dysfunction to diverse pathologies. The crystal structure of different Kir channels is opening the way to understanding the structure-function relationships of this simple but diverse ion channel family.

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Effects of barium, furosemide, ouabaine and 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS) on ionophoretically-induced changes in extracellular potassium concentration in hippocampal slices from rats and from patients with epilepsy

Cited by 63 publications

References 50 publications

Astrocyte dysfunction in temporal lobe epilepsy: K⁺ channels and gap junction coupling

Astrocyte dysfunction in temporal lobe epilepsy: K⁺ channels and gap junction coupling

The Impact of Astrocytic Gap Junctional Coupling on Potassium Buffering in the Hippocampus

Inwardly Rectifying Potassium Channels: Their Structure, Function, and Physiological Roles

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Effects of barium, furosemide, ouabaine and 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS) on ionophoretically-induced changes in extracellular potassium concentration in hippocampal slices from rats and from patients with epilepsy

Cited by 63 publications

References 50 publications

Astrocyte dysfunction in temporal lobe epilepsy: K+ channels and gap junction coupling

Astrocyte dysfunction in temporal lobe epilepsy: K+ channels and gap junction coupling

The Impact of Astrocytic Gap Junctional Coupling on Potassium Buffering in the Hippocampus

Inwardly Rectifying Potassium Channels: Their Structure, Function, and Physiological Roles

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Product

Resources

About

Astrocyte dysfunction in temporal lobe epilepsy: K⁺ channels and gap junction coupling

Astrocyte dysfunction in temporal lobe epilepsy: K⁺ channels and gap junction coupling