A study of the mechanisms by which potassium moves through brain tissue in the rat.

Gardner-Medwin, A. R.

doi:10.1113/jphysiol.1983.sp014539

Cited by 137 publications

(84 citation statements)

References 31 publications

(59 reference statements)

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“…For many years, the primary function attributed to gap junctions in glia was their contribution to K + homeostasis during neuronal activity (34), a mechanism called K + buffering. Moreover, a modeling study has shown that the GJC between astrocytes is 5× more likely to support the K + transport than the extracellular diffusion (35). In the OG, this well-known property of K + buffering could support neuronal activity, a mechanism boosted by the K + itself via its facilitating effect on Cx30-mediated GJC between astrocytes.…”

Section: Discussionmentioning

confidence: 99%

Plasticity of astroglial networks in olfactory glomeruli

Roux

Benchenane

Rothstein

et al. 2011

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

117

118

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Several recent findings have shown that neurons as well as astrocytes are organized into networks. Indeed, astrocytes are interconnected through connexin-formed gap junction channels allowing exchanges of ions and signaling molecules. The aim of this study is to characterize astrocyte network properties in mouse olfactory glomeruli where neuronal connectivity is highly ordered. Dyecoupling experiments performed in olfactory bulb acute slices (P16-P22) highlight a preferential communication between astrocytes within glomeruli and not between astrocytes in adjacent glomeruli. Such organization relies on the oriented morphology of glomerular astrocytes to the glomerulus center and the enriched expression of two astroglial connexins (Cx43 and Cx30) within the glomeruli. Glomerular astrocytes detect neuronal activity showing membrane potential fluctuations correlated with glomerular local field potentials. Accordingly, gap junctional coupling of glomerular networks is reduced when neuronal activity is silenced by TTX treatment or after early sensory deprivation. Such modulation is lost in Cx30 but not in Cx43 KO mice, indicating that Cx30-formed channels are the molecular targets of this activity-dependent modulation. Extracellular potassium is a key player in this neuroglial interaction, because (i) the inhibition of dye coupling observed in the presence of TTX or after sensory deprivation is restored by increasing [K + ] e and (ii) treatment with a K ir channel blocker inhibits dye spread between glomerular astrocytes. Together, these results demonstrate that extracellular potassium generated by neuronal activity modulates Cx30-mediated gap junctional communication between glomerular astrocytes, indicating that strong neuroglial interactions take place at this first relay of olfactory information processing.O lfactory glomeruli (OG) represent functional units where olfactory signals are first processed (1, 2). The combination of the anatomical organization and the functional activity results in a highly ordered spatial map of glomerular activation associated with each odor (3, 4). However, this well-described organization refers only to neuronal circuits, and information concerning astroglial connectivity is lacking. In the brain, astrocytes express the highest rate of connexins (Cxs), the protein constituents of gap junction channels that provide the molecular basis for direct cellto-cell communication. Though astrocytes were initially thought to form a glial syncitium, there is now evidence for a more specialized network organization (5). As increasing evidence argues for dynamic interactions between neurons and astrocytes (6), a coordinated population of astrocytes working in concert with neurons could contribute to sensory integration occurring in OG. The goal of this study is to determine how Cx-mediated intercellular communication in astrocytes is organized and modulated in this brain structure characterized by functional units. Features of OG astrocytes studied so far include their morphology (7,8), membrane...

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Section: Discussionmentioning

confidence: 99%

Plasticity of astroglial networks in olfactory glomeruli

Roux

Benchenane

Rothstein

et al. 2011

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

117

118

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“…changes (dashed lines) based on a model of K+ uptake and release associated with current flow through a syncytium of cells in brain tissue (Gardner-Medwin, 1983 b). The parameters for the tissue model are the same as those employed for comparisons with other types of data elsewhere (Gardner-Medwin, 1983a), with an assumed current density at the tissue surface of 16 ,A mm-2 (see below). Each of the calculated curves for Fig.…”

Section: Methodsmentioning

confidence: 99%

“…Another issue stems from the comparison made by Gardner-Medwin (1983a) of the observed K+ flux during current flow with the flux expected for purely extracellular transport. This comparison rests on the assumption that the brain extracellular space has approximately the normal composition attributed to it in the literature, with [K+] approximately 3 mm as in cerebrospinal fluid (Somjen, 1979).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Changes of extracellular potassium activity induced by electric current through brain tissue in the rat.

Gardner-Medwin¹,

Nicholson²

1983

The Journal of Physiology

Self Cite

125

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“…29 Resolution of the extracellular potassium load following SD is primarily a function of astrocytes. 30 The astrocyte behaves as a nearly perfect potassium electrode with local changes in membrane potential difference reflective of local potassium concentration. 31 Astrocytic spatial buffering of local changes in potassium enables neuronal transmembrane potential to be re-established for subsequent discharge.…”

Section: A New Mechanismmentioning

confidence: 99%

New concepts regarding cerebral vasospasm: glial-centric mechanisms

Mutch

2010

Can J Anesth/J Can Anesth

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Purpose Poor outcome in patients with cerebral vasospasm following subarachnoid hemorrhage remains a serious clinical problem. The current management with focus on the cerebrovascular constriction accounts for the use of ''triple-H'' therapy (hypertension, hypervolemia, and hemodilution) to enhance cerebral blood flow through constricted vessels. Recent work suggests that spreading depression (a stereotypical response of cerebral cortical tissue to noxious stimuli with subsequent oligemic blood flow) occurs in patients with cerebral vasospasm. A narrative review was conducted to examine the relationship between spreading depression and subarachnoid hemorrhage and to identify the anesthetic effects on the propagation of spreading depression. Principal findings Following review of the literature, an underlying mechanism is advanced that cerebral vasospasm is not primarily a problem of the cerebral vasculature but a consequence of glial cell dysfunction following spreading depression -a glial-centric cause for vasospasm. Such a mechanism for vasospasm becomes manifest when spreading depression waves transition to peri-infarct depolarization waves -with protracted ischemic blood flow in compromised tissue. The extracellular microenvironment with high potassium and low nitric oxide tension can account for conducting vessel narrowing. Conclusions The implication for clinical management is discussed supposing glial cell dysfunction is an underlying mechanism responsible for the vascular spasm. RésuméObjectif Les mauvais pronostics chez les patients manifestant un vasospasme ce´re´bral a`la suite d'une he´morragie sous-arachnoı¨dienne demeurent un proble`me clinique majeur. La prise en charge actuelle se concentre sur la constriction vasculaire ce´re´brale, ce qui explique le recours au traitement dit des « trois H » (hypertension, hypervole´mie et he´modilution) dans le but d'ame´liorer le de´bit sanguin ce´re´bral dans les vaisseaux contracte´s. Des recherches re´centes sugge`rent qu'une de´pression propage´e (une re´action typique du tissu cortical ce´re´bral aux stimuli nociceptifs, laquelle est suivie d'un de´bit sanguin re´duit) survient chez les patients manifestant un vasospasme ce´re´bral. Un compte-rendu narratif a e´te´entrepris afin d'examiner la relation entre la de´pression propage´e et l'he´morragie sous-arachnoı¨dienne ainsi que d'identifier les effets des anesthe´siques sur la propagation de la de´pression propage´e. Constatations principales Apre`s avoir passe´en revue la litte´rature sur le sujet, l'hypothe`se d'un me´canisme sous-jacent est avance´e, selon laquelle le vasospasme ce´re´bral n'est pas un proble`me principalement lie´a`la vasculature ce´re´brale mais plutôt la conse´quence d'un dysfonctionnement des cellules gliales apre`s une de´pression propage´e -en d'autres mots, le vasospasme est cause´principalement au niveau glial. Ce me´canisme qui provoque le vasospasme est manifeste lorsque les vagues de de´pression propage´e se changent en vagues de de´polarisation autour de l'infarct...

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A study of the mechanisms by which potassium moves through brain tissue in the rat.

Cited by 137 publications

References 31 publications

Plasticity of astroglial networks in olfactory glomeruli

Plasticity of astroglial networks in olfactory glomeruli

Changes of extracellular potassium activity induced by electric current through brain tissue in the rat.

New concepts regarding cerebral vasospasm: glial-centric mechanisms

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