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Targeting pannexin1 improves seizure outcome
Marcelo F Santiago1, Jana Veliskova, Naman K Patel
1The Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, New York, United States of America.
Plos One
|September 28, 2011
Summary
Pannexin1 (Panx1) channels contribute to seizures by increasing extracellular ATP. Blocking Panx1 activity in juvenile mice reduced seizure severity and duration, indicating its role in neuronal hyperactivity.
Area of Science:
- Neuroscience
- Cell Biology
- Epilepsy Research
Background:
- Seizures involve an imbalance of neurotransmitters like glutamate and GABA.
- Altered adenosine triphosphate (ATP) signaling is implicated in epilepsy, but release mechanisms are unclear.
- Pannexin1 (Panx1) channels, permeable to ATP, are highly expressed in the developing brain and activated by stimuli relevant to seizures.
Purpose of the Study:
- To investigate the role of Pannexin1 (Panx1) channels in ATP release during seizures.
- To determine if Panx1 activation contributes to neuronal hyperactivity and seizure progression.
- To evaluate the therapeutic potential of targeting Panx1 in epilepsy.
Main Methods:
- Utilized pharmacological inhibitors to block Pannexin1 (Panx1) channel activity.
- Employed two transgenic mouse models lacking functional Pannexin1 (Panx1).
- Induced seizures using kainic acid in juvenile mice to model status epilepticus.
Main Results:
- Interference with Pannexin1 (Panx1) channel function ameliorated the outcome of kainic acid-induced seizures.
- Blocking Pannexin1 (Panx1) activity significantly shortened the duration of status epilepticus.
- These findings demonstrate that activated Pannexin1 (Panx1) in juvenile mouse hippocampi contributes to seizure-induced neuronal hyperactivity.
Conclusions:
- Pannexin1 (Panx1) channels play a significant role in ATP release during seizures.
- Targeting Pannexin1 (Panx1) channels may offer a novel therapeutic strategy for epilepsy.
- The study highlights Pannexin1's contribution to neuronal hyperexcitability in the context of seizures.
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