Pannexin-1 channels within a neural network, symbolizing their role in epilepsy.

Epilepsy and Pannexin-1 Channels: Unlocking New Pathways for Treatment

Mira Elwood in Health & Wellness June 2025 • 4 min read.

"Explore the groundbreaking research on Pannexin-1 channels and their critical role in epilepsy, offering new hope for targeted therapies."

Epilepsy, characterized by recurrent seizures and related neurological activity, affects millions worldwide. This condition disrupts normal brain function, leading to an imbalance between excitation and inhibition in the brain. While factors such as brain lesions, tumors, and genetic abnormalities are known contributors, the intricate mechanisms of epileptogenesis remain a significant area of research.

Recent studies have shed light on the crucial role of pannexin-1 (Panx1) channels in epilepsy. These channels are now recognized as central players in the dynamics observed during epileptic activity. This article explores the latest advancements, controversies, and unresolved questions in Panx1 research related to epilepsy.

Panx1 channels primarily function as single-membrane, large-conductance channels regulated by various factors, including post-translational modifications and cellular localization. Found in both neurons and astroglia within the central nervous system (CNS), Panx1 mediates the release of adenosine 5'-triphosphate (ATP) and glutamate, key neurotransmitters in brain function.

How Does Pannexin-1 Contribute to Epilepsy?

Pannexin-1 channels within a neural network, symbolizing their role in epilepsy.

Although the exact mechanisms by which Panx1 contributes to epilepsy are still under investigation, several lines of evidence suggest a significant role in epileptogenesis. Research indicates that Panx1 expression is elevated in animal models of seizures and in resected human epileptic brain tissue, highlighting its relevance to epilepsy.

One study demonstrated that inducing epileptiform activity in mouse hippocampi led to an increase in Panx1 mRNA and significant post-translational modifications of the Panx1 protein. This activity was blocked by octanol, suggesting the involvement of gap junctions or pannexin channels. Furthermore, increased Panx1 expression has been observed in patients with Rasmussen Encephalitis and temporal lobe epilepsy, with Panx1 mRNA expression correlating with seizure frequency in focal cortical dysplasia.

Elevated Expression: Panx1 expression is raised in several animal models of seizure and is localized to regions critical for seizure development.
Multifaceted Role: Panx1 channels appear to have a multi-faceted and critical role in epileptogenesis, including contributions to P2X receptor activation, ATP release, glutamatergic signalling, and potassium dynamics.
Target for Therapies: Studies suggest that blocking Panx1 channels reduces excitability, can be anticonvulsant, and may be a promising target for future therapies.

In excitatory synapses, Panx1 channels are located near the postsynaptic density and astrocytes, exposing them to changes in membrane voltage, pH, and extracellular ionic conditions. These channels are regulated by factors such as extracellular potassium levels, zinc, intracellular calcium, and mechanical stimulation.

The Future of Pannexin-1 Research in Epilepsy

As research into Pannexin-1 channels continues to evolve, the connections between Panx1 and epilepsy become more evident. While the results may seem confounding, they highlight the complex role of Panx1 in seizure activity. A deeper understanding of these mechanisms at the cellular and molecular levels could pave the way for novel therapeutic interventions. Targeting Panx1 channels may offer a promising avenue for treating seizures and preventing epileptogenesis, bringing new hope to those affected by this challenging condition.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.neulet.2017.09.004, Alternate LINK

Title: Pannexin-1 Channels In Epilepsy

Subject: General Neuroscience

Journal: Neuroscience Letters

Publisher: Elsevier BV

Authors: Mark S. Aquilino, Paige Whyte-Fagundes, Georg Zoidl, Peter L. Carlen

Published: 2019-03-01

Everything You Need To Know

What is epilepsy?

Epilepsy is a neurological condition marked by recurrent seizures due to abnormal brain activity. This disruption stems from an imbalance between excitation and inhibition within the brain, and while various factors such as brain lesions and genetics contribute, the underlying mechanisms of epileptogenesis are complex and actively researched.

What are Pannexin-1 (Panx1) channels?

Pannexin-1 (Panx1) channels are single-membrane, large-conductance channels present in both neurons and astroglia within the central nervous system. These channels mediate the release of adenosine 5'-triphosphate (ATP) and glutamate, which are crucial neurotransmitters affecting brain function. They are regulated by several factors including post-translational modifications and cellular localization.

How does Pannexin-1 contribute to epilepsy?

Research indicates that Panx1 expression is elevated in animal models of seizures and in resected human epileptic brain tissue, suggesting a significant role in epileptogenesis. Studies have shown that inducing epileptiform activity increases Panx1 mRNA, which can be blocked by octanol. Increased Panx1 expression has also been observed in patients with conditions like Rasmussen Encephalitis and temporal lobe epilepsy. The channel's multifaceted role includes contributions to P2X receptor activation, ATP release, glutamatergic signalling, and potassium dynamics.

Why is Pannexin-1 a potential target for epilepsy treatments?

Targeting Pannexin-1 channels has emerged as a potential therapeutic strategy because studies suggest that blocking these channels can reduce excitability and may have anticonvulsant effects. Specifically, since Panx1 contributes to multiple pathways involved in seizures, modulating its activity could potentially mitigate seizure frequency and severity. This approach offers a promising avenue for new treatments to prevent epileptogenesis.

What is the future of Pannexin-1 research in relation to epilepsy?

Future research aims to deepen our understanding of the cellular and molecular mechanisms underlying Panx1's role in epilepsy. Understanding how these channels operate, the factors that regulate them, and how they contribute to seizure activity will allow for novel therapeutic interventions. The complexity of the role of Pannexin-1 in seizure activity requires a deeper understanding, which could lead to new targeted therapies that bring new hope to those affected by the condition.