Gap Junctions Regulate Seizure Activity – But in Unexpected Ways

Voss, Logan J.; Sleigh, James W.

doi:10.1016/b978-0-12-415901-3.00013-x

Cited by 2 publications

(3 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GJIC may act in an anticonvulsant manner by facilitating spatial K + and glutamate buffering, and extracellular space volume regulation. On the other hand, GJIC could promote ictogenesis by mediating nutrient transport to neurons to sustain synaptic activity and by facilitating the synchronization of neuronal electrical activity via astrocytic Ca 2+ astrocytic signaling [ 49 ]. One should be cautious to draw conclusions from KO studies, since in dKO mice, Cx30 and Cx43 are permanently deleted, HC and GJ channel functions are eliminated, non-channel functions also disappear, and other compensatory mechanisms are possible [ 125 , 126 , 130 , 131 ].…”

Section: Data Derived From Transgenic Micementioning

confidence: 99%

“…For this purpose, Cx43 mimetic peptides, i.e., short peptides identical to specific sequences of the Cx protein were used as tools to inhibit Cx43 channels in a more specific way. Cx43 mimetic peptides identical to sequences on the EL have been used to interfere with GJ formation during the docking of two HCs, a process that relies on well conserved EL sequences [ 49 , 180 ]. Two examples of such EL-mimetic peptides are Gap26 (VCYDKSFPISHVR) and Gap27 (SRPTEKTIFII).…”

Section: Effects Of CX Mimetic Peptides In Rodent Models Of Seizurmentioning

confidence: 99%

“…Cx43 GJs have a complex and ambiguous role in epilepsy and two (divergent) possibilities emanate from literature [ 49 ] ( Figure 1 ). Gap junctional intercellular communication (GJIC) is believed to be key in maintaining tissue homeostasis and in propagating electric and metabolic signals across cell populations [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Astrocytic Connexin43 Channels as Candidate Targets in Epilepsy Treatment

et al. 2020

View full text Add to dashboard Cite

In epilepsy research, emphasis is put on exploring non-neuronal targets such as astrocytic proteins, since many patients remain pharmacoresistant to current treatments, which almost all target neuronal mechanisms. This paper reviews available data on astrocytic connexin43 (Cx43) signaling in seizures and epilepsy. Cx43 is a widely expressed transmembrane protein and the constituent of gap junctions (GJs) and hemichannels (HCs), allowing intercellular and extracellular communication, respectively. A plethora of research papers show altered Cx43 mRNA levels, protein expression, phosphorylation state, distribution and/or functional coupling in human epileptic tissue and experimental models. Human Cx43 mutations are linked to seizures as well, as 30% of patients with oculodentodigital dysplasia (ODDD), a rare genetic condition caused by mutations in the GJA1 gene coding for Cx43 protein, exhibit neurological symptoms including seizures. Cx30/Cx43 double knock-out mice show increased susceptibility to evoked epileptiform events in brain slices due to impaired GJ-mediated redistribution of K+ and glutamate and display a higher frequency of spontaneous generalized chronic seizures in an epilepsy model. Contradictory, Cx30/Cx43 GJs can traffic nutrients to high-energy demanding neurons and initiate astrocytic Ca2+ waves and hyper synchronization, thereby supporting proconvulsant effects. The general connexin channel blocker carbenoxolone and blockers from the fenamate family diminish epileptiform activity in vitro and improve seizure outcome in vivo. In addition, interventions with more selective peptide inhibitors of HCs display anticonvulsant actions. To conclude, further studies aiming to disentangle distinct roles of HCs and GJs are necessary and tools specifically targeting Cx43 HCs may facilitate the search for novel epilepsy treatments.

show abstract