Contribution of non-selective membrane channels and receptors in epilepsy

Overcoming refractory epilepsy's resistance to the combination of antiepileptic drugs (AED), mitigating side effects, and preventing sudden unexpected death in epilepsy are critical goals for therapy of this disorder. Current therapeutic strategies are based primarily on neurocentric mechanisms...

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Published in:Pharmacology & therapeutics (Oxford) 2022-03, Vol.231, p.107980-107980, Article 107980
Main Authors: García-Rodríguez, Claudia, Bravo-Tobar, Iván D., Duarte, Yorley, Barrio, Luis C., Sáez, Juan C.
Format: Article
Language:English
Subjects:
CALHM1 channels
Connexins - metabolism
Epilepsy
Epilepsy - drug therapy
Epilepsy - metabolism
Hemichannels
Humans
Microglia - metabolism
Nerve Tissue Proteins - metabolism
Neurons - metabolism
P2X receptors
Seizures - metabolism
Transient Receptor Potential Channels - metabolism
TRP channels
VDACs
VRACs
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Summary:Overcoming refractory epilepsy's resistance to the combination of antiepileptic drugs (AED), mitigating side effects, and preventing sudden unexpected death in epilepsy are critical goals for therapy of this disorder. Current therapeutic strategies are based primarily on neurocentric mechanisms, overlooking the participation of astrocytes and microglia in the pathophysiology of epilepsy. This review is focused on a set of non-selective membrane channels (permeable to ions and small molecules), including channels and ionotropic receptors of neurons, astrocytes, and microglia, such as: the hemichannels formed by Cx43 and Panx1; the purinergic P2X7 receptors; the transient receptor potential vanilloid (TRPV1 and TRPV4) channels; calcium homeostasis modulators (CALHMs); transient receptor potential canonical (TRPC) channels; transient receptor potential melastatin (TRPM) channels; voltage-dependent anion channels (VDACs) and volume-regulated anion channels (VRACs), which all have in common being activated by epileptic activity and the capacity to exacerbate seizure intensity. Specifically, we highlight evidence for the activation of these channels/receptors during epilepsy including neuroinflammation and oxidative stress, discuss signaling pathways and feedback mechanisms, and propose the functions of each of them in acute and chronic epilepsy. Studying the role of these non-selective membrane channels in epilepsy and identifying appropriate blockers for one or more of them could provide complementary therapies to better alleviate the disease.
ISSN:0163-7258
1879-016X
DOI:10.1016/j.pharmthera.2021.107980