The role of gap junctions in seizures

Carlen, Peter L.; Skinner, Frances K.; Zhang, Liang; Naus, Christian C.; Kushnir, M.; Velázquez, José Luis Pérez

doi:10.1016/s0165-0173(99)00084-3

Cited by 160 publications

(96 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Electrical synapses also have essential roles in the developing brain, where they regulate the formation of chemical synapses (3)(4)(5). In humans, mutations that affect electrical synapses are associated with neurological conditions such as epilepsy, deafness, and peripheral neuropathies (6)(7)(8). However, it is difficult to study electrical synapses in detail because there are few simple functional assays or pharmacological tools that selectively target their activity.…”

mentioning

confidence: 99%

Dissection of neuronal gap junction circuits that regulate social behavior in Caenorhabditis elegans

Jang

Levy

Flavell

et al. 2017

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

View full text Add to dashboard Cite

A hub-and-spoke circuit of neurons connected by gap junctions controls aggregation behavior and related behavioral responses to oxygen, pheromones, and food in Caenorhabditis elegans. The molecular composition of the gap junctions connecting RMG hub neurons with sensory spoke neurons is unknown. We show here that the innexin gene unc-9 is required in RMG hub neurons to drive aggregation and related behaviors, indicating that UNC-9-containing gap junctions mediate RMG signaling. To dissect the circuit in detail, we developed methods to inhibit unc-9-based gap junctions with dominant-negative unc-1 transgenes. unc-1(dn) alters a stomatin-like protein that regulates unc-9 electrical signaling; its disruptive effects can be rescued by a constitutively active UNC-9::GFP protein, demonstrating specificity. Expression of unc-1(dn) in RMG hub neurons, ADL or ASK pheromone-sensing neurons, or URX oxygen-sensing neurons disrupts specific elements of aggregation-related behaviors. In ADL, unc-1(dn) has effects opposite to those of tetanus toxin light chain, separating the roles of ADL electrical and chemical synapses. These results reveal roles of gap junctions in a complex behavior at cellular resolution and provide a tool for similar exploration of other gap junction circuits.innexin | neural circuits | electrical synapses | stomatin | sensory behavior

show abstract

mentioning

confidence: 99%

Dissection of neuronal gap junction circuits that regulate social behavior in Caenorhabditis elegans

Jang

Levy

Flavell

et al. 2017

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

View full text Add to dashboard Cite

show abstract

“…However, different connexins have been identified in a same tissue or cell. For instance, Cx40, Cx43, and Cx45 are the three major connexins found in the myocardiac cells (Carlen et al, 2000), while Cx37, Cx40, and Cx43 are specific to VSMCs (Isakson et al, 2006). In normal vascular wall, the integrity of endothelial cells is essential for the maintenance of the physiology of blood vessels.…”

Section: Discussionmentioning

confidence: 99%

Effects of Losartan and Ramipril on the connexin expression in a rabbit balloon injury model

Li¹,

Li²,

Duan³

et al. 2011

Afr. J. Pharm. Pharmacol.

View full text Add to dashboard Cite

Intercellular gap junction (GJ) plays a pivotal role in the proliferation and transformation of vascular smooth muscle cells (VSMCs). This study was designed to test the hypothesis that expressions of the component proteins of gap junctions, connexins40 and 43 (Cx40 and Cx43), are up-regulated in arteries subjected to balloon injury and that this up-regulation can be suppressed by statin therapy. Transmission electron microscopy (TEM) revealed that there were abundant GJ between neointimal SMCs but fewer and smaller GJ after losartan and ramipril treatment. Reverse transcription-polymerase chain reaction and Western blot analysis showed the messenger ribonucleic acid (mRNA) and protein expressions of Cx40 and Cx43 were elevated after injury, and these elevations were suppressed by losartan and ramipril. Immunostaining showed the Cx40 and Cx43 expressions were consistently enhanced in the neointimal area after injury, which was decreased by losartan and ramipril treatment. Balloon injury causes up-regulation of Cx40 and Cx43 in neointimal SMCs. angiotensin-converting enzyme inhibitors (ACEIs) and AT 1 antagonist losartan can reduce the proliferation of SMCs, suggesting the rennin-angiotensin system (RAS) system plays an important role in the remodeling of GJ in the VSMCs under pathological conditions.

show abstract

“…17 No modelo Ca +2 -zero de sincronia neural com bloqueio das sinapses químicas foram encontradas evidências de efeitos pró-convulsivos das JC. 8 Os resultados mostram que manipulações que diminuem a condutância das JC, incluindo aplicação de halotano, octanol e redução do pH intracelular, também reduzem a atividade epiléptica induzida pelo Ca +2 -zero. 8,21 De forma oposta, as descargas epilépticas foram potencializadas pelo aumento do pH intracelular, com o uso de bicarbonato, TMA 8,21,22 e cloreto de amônia.…”

Section: Figura 1 Junções Comunicantesunclassified

Papel das sinapses elétricas em crises epilépticas

Silva¹,

Bachiega-Salviano²,

Zanetti³

et al. 2010

J. epilepsy clin. neurophysiol.

View full text Add to dashboard Cite

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...

show abstract

The role of gap junctions in seizures

Cited by 160 publications

References 67 publications

Dissection of neuronal gap junction circuits that regulate social behavior in Caenorhabditis elegans

Dissection of neuronal gap junction circuits that regulate social behavior in Caenorhabditis elegans

Effects of Losartan and Ramipril on the connexin expression in a rabbit balloon injury model

Papel das sinapses elétricas em crises epilépticas

Contact Info

Product

Resources

About