Cellular mechanisms of potassium homeostasis in the mammalian nervous system

Grafe, Peter; Ballanyi, Klaus

doi:10.1139/y87-164

Cited by 32 publications

(23 citation statements)

References 15 publications

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“…We must, however, emphasize that different clearance mechanisms may dominate in other brain regions. Increased Na 1 /K 1 -ATPase activity generates intracellular K 1 accumulation and its molecular characteristics therefore aligns well with the reported transient increase in intracellular K 1 concentration of astrocytes during the burst of activity which, however, is immediately followed by post-stimulus restoration of neuronal [K 1 ] i Grafe and Ballanyi, 1987). The a2b2 isoform constellation characteristic to Na 1 /K 1 -ATPase in glial cells appears to be specifically geared to respond to excess extracellular K 1 due to its lower K 1 affinity and higher voltage-sensitivity.…”

Section: Discussionsupporting

confidence: 85%

“…Therefore, regulation of extracellular K + concentration ([K + ] o ) is of vital importance for neuronal function. In vitro studies have shown that stimulation-induced increases in [K + ] are paralleled by accumulation of K + in astrocytes, suggesting an astrocytic contribution to [K + ] o regulation (Ballanyi et al 1987; Grafe and Ballanyi 1987). Neuronal activity is, in addition, associated with shrinkage of the extracellular space (Dietzel et al 1980; Ransom et al 1985) probably due to astrocytic swelling (MacVicar et al 2002).…”

Section: Introductionmentioning

confidence: 99%

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Contributions of the Na⁺/K⁺‐ATPase, NKCC1, and Kir4.1 to hippocampal K⁺ clearance and volume responses

Larsen

Assentoft

Cotrina

et al. 2014

Glia

220

309

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Bursts of network activity in the brain are associated with a transient increase in extracellular K+ concentration. The excess K+ is removed from the extracellular space by mechanisms proposed to involve Kir4.1-mediated spatial buffering, the Na+/K+/2Cl− cotransporter (NKCC1), and/or Na+/K+-ATPase activity. Their individual contribution to [K+]o management has been of extended controversy. The present study aimed, by several complementary approaches, to delineate the transport characteristics of Kir4.1, NKCC1, and Na+/K+-ATPase and to resolve their involvement in clearance of extracellular K+ transients. Primary cultures of rat astrocytes displayed robust NKCC1 activity with [K+]o increases above basal levels. Increased [K+]o produced NKCC1-mediated swelling of cultured astrocytes and NKCC1 could thereby potentially act as a mechanism of K+ clearance while concomitantly mediate the associated shrinkage of the extracellular space. In rat hippocampal slices, inhibition of NKCC1 failed to affect the rate of K+ removal from the extracellular space while Kir4.1 enacted its spatial buffering only during a local [K+]o increase. In contrast, inhibition of the different isoforms of Na+/K+-ATPase reduced post-stimulusclearance of K+ transients. The glia-specific α2/β2 subunit composition of Na+/K+-ATPase, when expressed in Xenopus oocytes, displayed a K+ affinity and voltage-sensitivity that would render this astrocyte-specific subunit composition specifically geared for controlling [K+]o during neuronal activity. In rat hippocampal slices, simultaneous measurements of the extracellular space volume revealed that neither Kir4.1, NKCC1, nor Na+/K+-ATPase accounted for the stimulus-induced shrinkage of the extracellular space. Thus, NKCC1 plays no role in activity-induced extracellular K+ recovery in native hippocampal tissue while Kir4.1 and Na+/K+-ATPase serve temporally distinct roles.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Contributions of the Na⁺/K⁺‐ATPase, NKCC1, and Kir4.1 to hippocampal K⁺ clearance and volume responses

Larsen

Assentoft

Cotrina

et al. 2014

Glia

220

309

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“…It is generally believed that the b-wave is the extracellular expression of radial current flow generated by a potassium-mediated depolarization of the Muller cells (28)(29)(30) (38,39). Both the permeability of the cell membrane to potassium and energydependent processes are thought to participate in maintaining the stability ofthe extracellular potassium concentration (40). The glial cell reaction to the neuronal release of GABA may represent another component in this homeostatic system.…”

Section: Resultsmentioning

confidence: 99%

gamma-Aminobutyric acid (GABA)-induced currents of skate Muller (glial) cells are mediated by neuronal-like GABAA receptors.

Malchow

Qian

Ripps

1989

Proc. Natl. Acad. Sci. U.S.A.

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Radial glia (Muller cells) of the vertebrate retina appear to be intimately involved in regulating the actions of amino acid neurotransmitters. One of the amino acids thought to be important in mediating retinal information flow is y-aminobutyric acid (GABA). The rmdings of this study indicate that enzymatically isolated skate Muller cells are depolarized by GABA and the GABAA agonist muscimol and that the actions of these agents are reduced by bicuculline and picrotoxin. Membrane currents induced by GABA under voltage clamp were dose dependent, were associated with an increase in membrane conductance, and showed marked desensitization when the concentration of GABA exceeded 2.5ImM. The responses had a reversal potential close to that calculated for chloride, indicating that the currents were generated by ions passing through channels. These data support the view that skate Muller cells possess functional GABAA receptors. The presence of such receptors on retinal glia may have important implications for the role of Muller cells in maintaining the constancy of the extracellular milieu, for neuron-glia interactions within the retina, and for theories concerning the generation of the electroretinogram.Glial cells can no longer be thought of as the "silent supporters" of neurons-i.e., electrically inexcitable elements whose passive properties serve to maintain the constancy of the extracellular milieu. Several voltage-sensitive currents have been ascribed to various types of glia throughout the nervous system (1-3), and there is evidence to indicate that the cellular potential of glial cells can be altered by electrogenic uptake mechanisms (4) as well as by ligand-gated ionophores (5). However, depending on the species and type of glial element, there is a striking heterogeneity in the nature of the voltage-dependent channels (6), the cellular responses to neurotransmitters (7,8), and the underlying mechanisms mediating these reactions (9, 10).We report here that a similar heterogeneity is evident in the electrical behavior of the radial glia (Muller cells) of the vertebrate retina, in particular with respect to their responses to the retinal neurotransmitters glutamatq and y-aminobutyric acid (GABA). Brew and Attwell (11) have shown that glutamate evokes a large inward current in isolated voltageclamped Muller cells of axolotl and provide evidence that the current is due to an electrogenic glutamate uptake mechanism activated by intracellular potassium (12). Results of the present study show that skate Muller cells are relatively insensitive to glutamate, whereas GABA induces large current responses that are mediated primarily by a neuronal-like receptor mechanism. MATERIALS AND METHODSCell Dissociation. Skate (Raja erinacea and Raja oscellata) were obtained from the Marine Biological Laboratory (Woods Hole, MA) and maintained for periods of up to 1 month in a tank of circulating artificial seawater held at 14'C; a 12-hr light/dark cycle was used. Prior to enucleation, animals were dark adapted for 1.5 hr, ...

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“…The neighbouring astrocytes act as temporary K + sinks primarily via the action of the Na + /K + ‐ATPase and, to a smaller extent, the K + channel Kir4.1 (Ballanyi et al . ; Grafe & Ballanyi, ; Ransom et al . ; Kofuji & Newman, ; MacAulay & Zeuthen, ; Larsen et al .…”

Section: Discussionmentioning

confidence: 99%

“…The neighbouring astrocytes act as K + sinks during neuronal activity and take up a portion of the neuronally‐released K + (Ballanyi et al . ; Grafe & Ballanyi, ), predominantly via the glia‐specific K + ‐sensitive α2β2 isoform combination of the Na + /K + ‐ATPase, which is kinetically geared to respond to increased [K + ] o and the associated membrane depolarization (Ransom et al . ; D'Ambrosio et al .…”

Section: Introductionmentioning

confidence: 99%

Developmental maturation of activity‐induced K⁺ and pH transients and the associated extracellular space dynamics in the rat hippocampus

Larsen

Stoica

MacAulay

2018

The Journal of Physiology

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Key points Neuronal activity induces fluctuation in extracellular space volume, [K+]o and pHo, the management of which influences neuronal function The neighbour astrocytes buffer the K+ and pH and swell during the process, causing shrinkage of the extracellular space In the present study, we report the developmental rise of the homeostatic control of the extracellular space dynamics, for which regulation becomes tighter with maturation and thus is proposed to ensure efficient synaptic transmission in the mature animals The extracellular space dynamics of volume, [K+]o and pHo evolve independently with developmental maturation and, although all of them are inextricably tied to neuronal activity, they do not couple directly. Abstract Neuronal activity in the mammalian central nervous system associates with transient extracellular space (ECS) dynamics involving elevated K+ and pH and shrinkage of the ECS. These ECS properties affect membrane potentials, neurotransmitter concentrations and protein function and are thus anticipated to be under tight regulatory control. It remains unresolved to what extent these ECS dynamics are developmentally regulated as synaptic precision arises and whether they are directly or indirectly coupled. To resolve the development of homeostatic control of [K+]o, pH, and ECS and their interaction, we utilized ion‐sensitive microelectrodes in electrically stimulated rat hippocampal slices from rats of different developmental stages (postnatal days 3–28). With the employed stimulation paradigm, the stimulus‐evoked peak [K+]o and pHo transients were stable across age groups, until normalized to neuronal activity (field potential amplitude), in which case the K+ and pH shifted significantly more in the younger animals. By contrast, ECS dynamics increased with age until normalized to the field potential, and thus correlated with neuronal activity. With age, the animals not only managed the peak [K+]o better, but also displayed swifter post‐stimulus removal of [K+]o, in correlation with the increased expression of the α1‐3 isoforms of the Na+/K+‐ATPase, and a swifter return of ECS volume. The different ECS dynamics approached a near‐identical temporal pattern in the more mature animals. In conclusion, although these phenomena are inextricably tied to neuronal activity, our data suggest that they do not couple directly.

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Cellular mechanisms of potassium homeostasis in the mammalian nervous system

Cited by 32 publications

References 15 publications

Contributions of the Na⁺/K⁺‐ATPase, NKCC1, and Kir4.1 to hippocampal K⁺ clearance and volume responses

Contributions of the Na⁺/K⁺‐ATPase, NKCC1, and Kir4.1 to hippocampal K⁺ clearance and volume responses

gamma-Aminobutyric acid (GABA)-induced currents of skate Muller (glial) cells are mediated by neuronal-like GABAA receptors.

Developmental maturation of activity‐induced K⁺ and pH transients and the associated extracellular space dynamics in the rat hippocampus

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Cellular mechanisms of potassium homeostasis in the mammalian nervous system

Cited by 32 publications

References 15 publications

Contributions of the Na+/K+‐ATPase, NKCC1, and Kir4.1 to hippocampal K+ clearance and volume responses

Contributions of the Na+/K+‐ATPase, NKCC1, and Kir4.1 to hippocampal K+ clearance and volume responses

gamma-Aminobutyric acid (GABA)-induced currents of skate Muller (glial) cells are mediated by neuronal-like GABAA receptors.

Developmental maturation of activity‐induced K+ and pH transients and the associated extracellular space dynamics in the rat hippocampus

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Resources

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Contributions of the Na⁺/K⁺‐ATPase, NKCC1, and Kir4.1 to hippocampal K⁺ clearance and volume responses

Contributions of the Na⁺/K⁺‐ATPase, NKCC1, and Kir4.1 to hippocampal K⁺ clearance and volume responses

Developmental maturation of activity‐induced K⁺ and pH transients and the associated extracellular space dynamics in the rat hippocampus