Involvement of electrical coupling in the in vivo ictal epileptiform activity induced by 4-aminopyridine in the neocortex

Szente, Magdolna; Gajda, Zita; Ali, K. Said; Hermesz, Edit

doi:10.1016/s0306-4522(02)00533-x

Cited by 105 publications

(85 citation statements)

References 67 publications

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“…In this study, we attempted to explore whether specific gap-junction blockers affect the cellular sensitivity to ischemic injury in rats and whether such blockade diminishes the diffusion of reactive oxygen species (ROS) in vitro. Carbenoxolone (CBX) is effective in blocking gap-junction coupling [15] , interferes little with synaptic function in vivo and in vitro [16][17][18][19] , and induces minimal changes in intrinsic neuronal characteristics [20,21] .…”

Section: Introductionmentioning

confidence: 99%

Protective effects of carbenoxolone are associated with attenuation of oxidative stress in ischemic brain injury

Zhang

Jing

et al. 2013

Neurosci. Bull.

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Accumulating evidence has suggested that the gap junction plays an important role in the determination of cerebral ischemia, but the underlying mechanisms remain to be elucidated. In this study, we assessed the effect of a gap-junction blocker, carbenoxolone (CBX), on ischemia/reperfusion-induced brain injury and the possible mechanisms. By using the transient cerebral ischemia model induced by occlusion of the middle cerebral artery for 30 min followed by reperfusion for 24 h, we found that pre-administration of CBX (25 mg/kg, intracerebroventricular injection, 30 min before cerebral ischemic surgery) diminished the infarction size in rats. And this was associated with a decrease of reactive oxygen species generation and inhibition of the activation of astrocytes and microglia. In PC12 cells, H 2 O 2 treatment induced more coupling and apoptosis, while CBX partly inhibited the opening of gap junctions and improved the cell viability. These results suggest that cerebral ischemia enhances the opening of gap junctions. Blocking the gap junction with CBX may attenuate the brain injury after cerebral ischemia/reperfusion by partially contributing to amelioration of the oxidative stress and apoptosis.

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Section: Introductionmentioning

confidence: 99%

Protective effects of carbenoxolone are associated with attenuation of oxidative stress in ischemic brain injury

Zhang

Jing

et al. 2013

Neurosci. Bull.

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“…Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Putative GJ blockers, such as octanol, halothane, heptanol, and CarbX, exert anticonvulsant actions in a variety of experimental seizure models [10,11,18,21,29]. For example, CarbX suppresses spontaneous epileptiform activity caused by enhanced neuronal excitability in area CA3 of hippocampus [21].…”

Section: Introductionmentioning

confidence: 99%

“…For example, CarbX suppresses spontaneous epileptiform activity caused by enhanced neuronal excitability in area CA3 of hippocampus [21]. Past studies have shown that epileptiform activity up-regulates GJ proteins [19,29] and increases electrotonic coupling [5], which would further facilitate the propagation and maintenance of synchronous network activity. GJ blockers presumably counter such enhancements to electrotonic communication, which may partly explain their anticonvulsant actions.…”

Section: Introductionmentioning

confidence: 99%

Carbenoxolone modifies spontaneous inhibitory and excitatory synaptic transmission in rat somatosensory cortex

Yang

Ling

2007

Neuroscience Letters

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Gap junction (GJ) coupling between neocortical GABAergic interneurons plays a critical role in the synchronization of activity in cortical networks in physiological and pathophysiological states, e.g., seizures. Past studies have shown that GJ blockers exert anticonvulsant actions in both in vivo and in vitro models of epilepsy. However, the precise mechanisms underlying these antiepileptic effects have not been fully elucidated. This is due, in part, to a lack of information of the influence of GJ blockade on network activity in the absence of convulsant agents or enhanced neuronal excitation. One key question is whether GJ blockers act on excitatory or inhibitory systems, or both. To address this issue, we examined the effects of the GJ blocker carbenoxolone (CarbX, 150 μM) on spontaneous inhibitory postsynaptic currents (sIPSCs) and excitatory postsynaptic currents (sEPSCs) in acute slices of rat somatosensory cortex. Results showed that CarbX decreased the amplitude and frequency of sIPSCs by 30.2% and 25.7%, respectively. CarbX increased the mean frequency of sEPSCs by 24.1%, but had no effect on sEPSC amplitude. During blockade of GABA A -mediated events with picrotoxin (20 μM), CarbX induced only a small increase in sEPSC frequency that was not statistically different from control, indicating CarbX enhancement of sEPECs was secondary to the depression of synaptic inhibition. These findings suggest that in neocortex, blockade of GJs leads to an increase in spontaneous excitation by uncoupling GABAergic interneurons, and that electronic communication between inhibitory cells plays a significant role in regulating tonic synaptic excitation. Keywordscarbenoxolone; gap junction; neocortex; EPSC; IPSC; in vitro Neural communication through gap junctions (GJs) plays an important role in the generation and maintenance of synchronized neuronal network activity in both physiological and pathophysiological conditions, e.g., seizures [26]. Morphological and electrophysiological evidence indicate that electrotonic coupling between GABAergic interneurons exists widely in the cortex [6], and plays a critical role in the synchronization of network activity. Repetitive stimulation of hippocampal circuits induces GABAergic synchronization which is blocked by carbenoxolone (CarbX), a putative GJ uncoupler [9]. In hippocampus [2,23] and neocortex [3,13], 4-aminopyridine (4-AP) induces synchronized GABAergic network activity that is independent of ionotropic glutamate receptor activation, but is suppressed by GJ blockade. * Corresponding author: Tel: 718-270-3804; Fax: 718-270-2241 E-mail: lie.yang@downstate.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which ...

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“…Com estes resultados, os autores concluem que a comunicação elétrica via JC colabora para a sincronia neuronal durante a atividade epileptiforme do neocórtex de ratos. 27 Os efeitos do bloqueio das JC nas atividades epileptiformes no modelo genético de epilepsia de ausência …”

Section: Figura 1 Junções Comunicantesunclassified

“…Com estes resultados, os autores concluem que a comunicação elétrica via JC colabora com a sincronia neuronal na atividade epiléptica do neocórtex de ratos. 27 …”

Section: Expressão Das Conexinas Nas Crises Modelos Animaisunclassified

Papel das sinapses elétricas em crises epilépticas

Silva¹,

Bachiega-Salviano²,

Zanetti³

et al. 2010

J. epilepsy clin. neurophysiol.

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RESumoIntrodução: No sistema nervoso central a comunicação entre neurônios se realiza através de estruturas denominadas sinapses: elétricas ou químicas. As sinapses elétricas são formadas pela aproximação das membranas plasmáticas de dois neurônios formando estruturas chamadas junções comunicantes (gap junctions, do inglês). As junções comunicantes são compostas por seis subunidades da proteína conexina de cada membrana, formando poros que comunicam o citoplasma de células adjacentes e permitem a passagem de íons e pequenas moléculas. objetivos: A presente revisão pretende descrever e discutir os principais resultados que apontam para uma importante relação entre junções comunicantes e sincronia neuronal durante crises epilépticas. Resultados e Conclusão: Quando um neurônio é despolarizado, este tipo de comunicação permite a rápida transferência iônica entre as células, promovendo alta sincronia neuronal. Recentemente, o papel das junções comunicantes na geração e propagação de descargas epilépticas tem sido estudado através do uso de diferentes modelos experimentais in vivo, in vitro e in silico (modelos computacionais).unitermos: Junções comunicantes, sinapse elétrica, conexinas, crises epilépticas. AbStRACtThe role of eletrical synapses in epileptic seizures Introduction: In the central nervous system, neuronal communication is accomplished by structures called synapses: electrical or chemical. Electrical synapses are formed by the apposition of plasmatic membranes at gap junctions and the interaction of connexin subunits from two neurons. At this site, connexin complexes create intercellular pores that communicate the cytoplasm of adjacent neurons and allow free flow of ions and small molecules. objective: In this review, we will present and discuss recent results showing the possible involvement of electrical synapses in the neuronal hypersynchronization during epileptic seizures. Results and conclusion: When a neuron is depolarized, ions flow very rapidly from one cell to the other promoting high neuronal synchrony. More recently, the role of gap junctions in the generation and propagation of epileptic discharges has been investigated using combined approaches of in vivo, in vitro and in silico (computational) models. Keyword: Gap junctions, eletrical synapses, connexin and epileptic seizures IntRoduçãoAs investigações sobre junções comunicantes (JC) no sistema nervoso têm uma longa história, iniciando com um primeiro estudo reportando a comunicação direta e acoplamento elétrico entre células nervosas de invertebrados. 11 Este trabalho pioneiro abriu caminho para muitos outros que estabeleceram a comunicação elétrica entre neurônios, a chamada de sinapse elétrica, como distinta da neurotransmissão química. 4 Subsequentemente, vários estudos demonstraram que as sinapses elétricas não estavam restritas a invertebrados, mas também podiam ser encontradas em vertebrados, incluindo os mamíferos. 3 Hoje sabemos que há dois tipos de sinapses no sistema nervoso central (SNC): as sinapses elétricas e as sinapses quí...

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Involvement of electrical coupling in the in vivo ictal epileptiform activity induced by 4-aminopyridine in the neocortex

Cited by 105 publications

References 67 publications

Protective effects of carbenoxolone are associated with attenuation of oxidative stress in ischemic brain injury

Protective effects of carbenoxolone are associated with attenuation of oxidative stress in ischemic brain injury

Carbenoxolone modifies spontaneous inhibitory and excitatory synaptic transmission in rat somatosensory cortex

Papel das sinapses elétricas em crises epilépticas

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