Ion Regulation in the Brain: Implications for Pathophysiology

Somjen, George G.

doi:10.1177/1073858402008003011

Cited by 298 publications

(115 citation statements)

References 135 publications

(81 reference statements)

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“…the interstitial and cerebrospinal fluids-ISF and CSF, respectively) is essential for normal central nervous system (CNS) function [38]. The regulation of K + appears to be particularly critical because small changes in K + concentrations have profound effects on neuronal activity.…”

Section: Introductionmentioning

confidence: 99%

Kv1 and Kir2 potassium channels are expressed in rat brain endothelial cells

Millar

Wang

Brown

et al. 2007

Pflugers Arch - Eur J Physiol

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The endothelial cells of the brain microvasculature, which constitute the blood-brain barrier, secrete K+ into brain interstitial fluid. K+ channels are predicted to have a central role to play in this process. The aim of the following study was to characterise K+ channels in primary cultures of endothelial cells isolated from rat brain microvessels by whole-cell patch clamp and real-time polymerase chain reaction. In the 4 h after plating, the rat brain endothelial cells expressed predominantly a depolarisation-activated delayed-rectifying outward K+ conductance and a time-independent inwardly rectifying K+ conductance prominent at hyperpolarising potentials. The outward current was inhibited by 1 mM 4-aminopyridine (4AP), 10 nM margatoxin and 100 nM dendrotoxin-K, indicating the involvement of Kv1 channels. The half maximal activation voltage and time constants of activation and inactivation of the 4AP-sensitive current were similar to Kv1.3. The inwardly rectifying conductance was inhibited by Ba2+ in a dose- and voltage-dependent fashion; the kinetics of which resembled Kir2 channels. Quantification of messenger ribonucleic acid transcripts revealed Kv1.3>1.2=1.4=1.5=1.6 and Kir2.1=2>2.3. In current-clamp experiments, both 4AP and Ba2+ depolarised the membrane potential. In conclusion, rat brain endothelial cells express Kv1 and Kir2 K+ channels, both of which participate in setting membrane potential and could mediate K+ secretion into the brain interstitial fluid.

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Section: Introductionmentioning

confidence: 99%

Kv1 and Kir2 potassium channels are expressed in rat brain endothelial cells

Millar

Wang

Brown

et al. 2007

Pflugers Arch - Eur J Physiol

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“…Early during an ictal discharge, the cerebral [K + ] EC increases to 7-12 m M and remains more or less steady at this elevated level [69][70][71] , with dynamics similar to that of the CBF increase in the adult [72] . The K + concentration in the newborn brain also increases to 3-7 m M above the baseline during seizures, but the rise and decay times of the [K + ] EC changes are longer and their amplitudes smaller than those in adults [67,73,74] ( fig.…”

Section: Potassiummentioning

confidence: 94%

Seizure-Induced Alterations in Cerebrovascular Function in the Neonate

2008

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Epileptiform seizures are most common during the neonatal period, affecting at least 0.3% of term neonates and more than 10% of preterm neonates. The adverse impact of neonatal seizures on the long-term neurological outcome has been well documented, but their cerebrovascular consequences are rarely emphasized. The cerebral blood flow is controlled by the interaction of the vascular and parenchymal cells forming the neurovascular unit via multiple mediator systems that have unique features in the newborn. Seizures drastically affect the neurovascular unit, resulting in (1) dramatic increases in brain metabolism and cerebral blood flow during the ictal period, (2) disruption of the blood-brain barrier, (3) an acute loss of cerebral pressure autoregulation, and (4) a delayed impairment of cerebrovascular reactivity to various stimuli. Furthermore, seizures frequently accompany and potentially aggravate a pre-existing cerebrovascular insult. This review summarizes the current knowledge on how seizures affecting various cells in the neurovascular unit result in the observed alterations in cerebrovascular function in the neonate.

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“…4). increases transiently during neuronal activity, but is prolonged elevated during epileptic seizures [32]. Furthermore, cell death by injuries or neurodegenerative diseases liberates intracellular K + .…”

Section: Discussionmentioning

confidence: 99%

Chloride Influx Provokes Lamellipodium Formation in Microglial Cells

Zierler

Frei

Grissmer

et al. 2008

Cell Physiol Biochem

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Lamellipodium extension and retraction is the driving force for cell migration. Although several studies document that activation of chloride channels are essential in cell migration, little is known about their contribution in lamellipodium formation. To address this question, we characterized chloride channels and transporters by whole cell recording and RT-PCR, respectively, as well as quantified lamellipodium formation in murine primary microglial cells as well as the microglial cell-line, BV-2, using time-lapse microscopy. The repertoire of chloride conducting pathways in BV-2 cells included, swelling-activated chloride channels as well as the KCl cotransporters, KCC1, KCC2, KCC3, and KCC4. Swelling-activated chloride channels were either activated by a hypoosmotic solution or by a high KCl saline, which promotes K⁺ and Cl^- influx instead of efflux by KCCs. Conductance through swelling-activated chloride channels was completely blocked by flufenamic acid (200μM), SITS (1mM) and DIOA (10μM). By exposing primary microglial cells or BV-2 cells to a high KCl saline, we observed a local swelling, which developed into a prominent lamellipodium. Blockade of chloride influx by flufenamic acid (200μM) or DIOA (10μM) as well as incubation of cells in a chloride-free high K⁺ saline suppressed formation of a lamellipodium. We assume that local swellings, established by an increase in chloride influx, are a general principle in formation of lamellipodia in eukaryotic cells.

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Ion Regulation in the Brain: Implications for Pathophysiology

Cited by 298 publications

References 135 publications

Kv1 and Kir2 potassium channels are expressed in rat brain endothelial cells

Kv1 and Kir2 potassium channels are expressed in rat brain endothelial cells

Seizure-Induced Alterations in Cerebrovascular Function in the Neonate

Chloride Influx Provokes Lamellipodium Formation in Microglial Cells

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