2018
DOI: 10.1016/j.nbd.2017.10.011
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Role of KCC2-dependent potassium efflux in 4-Aminopyridine-induced Epileptiform synchronization

Abstract: A balance between excitation and inhibition is necessary to maintain stable brain network dynamics. Traditionally, seizure activity is believed to arise from the breakdown of this delicate balance in favor of excitation with loss of inhibition. Surprisingly, recent experimental evidence suggests that this conventional view may be limited, and that inhibition plays a prominent role in the development of epileptiform synchronization. Here, we explored the role of the KCC2 co-transporter in the onset of inhibitor… Show more

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Cited by 26 publications
(25 citation statements)
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“…Therefore, increasing the Cl − extrusion capacity of KCC2 could have the opposite effect and reduce the likelihood of developing epileptiform discharges. However, it has been proposed that KCC2 actually facilitates Cl − loading during seizures due to a reversal in KCC2 transport direction caused by rises in [K + ] o (10,(22)(23)(24)(25)(26)(27). A role for KCC2 as either proconvulsant or anticonvulsant therefore remains controversial.…”
mentioning
confidence: 99%
“…Therefore, increasing the Cl − extrusion capacity of KCC2 could have the opposite effect and reduce the likelihood of developing epileptiform discharges. However, it has been proposed that KCC2 actually facilitates Cl − loading during seizures due to a reversal in KCC2 transport direction caused by rises in [K + ] o (10,(22)(23)(24)(25)(26)(27). A role for KCC2 as either proconvulsant or anticonvulsant therefore remains controversial.…”
mentioning
confidence: 99%
“…Recent evidence has suggested that the potassium-chloride co-transporter isoform 2 (KCC2) may play a key role in the generation of 4AP-induced epileptiform activity [ 15 , 17 - 19 , 22 ]. We hypothesized that the reduction of KCC2 activity by KCC2 antagonist VU0240551 may reduce the complexity of epileptiform activity elicited at higher concentrations of 4AP, resulting in more stereotyped epileptiform activity across various 4AP concentrations.…”
Section: Resultsmentioning
confidence: 99%
“…Recent work has pointed to the role of the KCC2 co-transporter in the development of 4AP-induced seizure [ 15 , 17 - 19 , 22 ]. KCC2-dependent efflux and accumulation of extracellular K + may drive transitions to a seizure-state by initiating a positive feedback loop in which elevated K + leads to network depolarization, which in turn leads to further accumulation of extracellular K + [ 17 , 23 , 35 - 40 ]. Previous studies have shown that 4AP-induced ictal, seizure-like activity can be abolished in response to reduced KCC2 co-transporter activity [ 18 ].…”
Section: Discussionmentioning
confidence: 99%
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