PUBLICATION
Panx1 channels promote both anti- and pro-seizure-like activities in the zebrafish via p2rx7 receptors and ATP signaling
- Authors
- Whyte-Fagundes, P., Taskina, D., Safarian, N., Zoidl, C., Carlen, P.L., Donaldson, L.W., Zoidl, G.R.
- ID
- ZDB-PUB-220520-2
- Date
- 2022
- Source
- Communications biology 5: 472 (Journal)
- Registered Authors
- Safarian, Nickie, Taskina, Daria, Whyte-Fagundes, Paige, Zoidl, Christiane, Zoidl, Georg
- Keywords
- none
- MeSH Terms
-
- Adenosine Triphosphate/metabolism
- Animals
- Connexins*/metabolism
- Nerve Tissue Proteins/metabolism
- Receptors, Purinergic P2X7*/metabolism
- Seizures/genetics
- Seizures/metabolism
- Signal Transduction
- Xenopus Proteins*/metabolism
- Zebrafish
- PubMed
- 35585187 Full text @ Commun Biol
Citation
Whyte-Fagundes, P., Taskina, D., Safarian, N., Zoidl, C., Carlen, P.L., Donaldson, L.W., Zoidl, G.R. (2022) Panx1 channels promote both anti- and pro-seizure-like activities in the zebrafish via p2rx7 receptors and ATP signaling. Communications biology. 5:472.
Abstract
The molecular mechanisms of excitation/inhibition imbalances promoting seizure generation in epilepsy patients are not fully understood. Evidence suggests that Pannexin1 (Panx1), an ATP release channel, modulates the excitability of the brain. In this report, we performed electrophysiological, behavioral, and molecular phenotyping experiments on zebrafish larvae bearing genetic or pharmacological knockouts of Panx1a and Panx1b channels, each homologous to human PANX1. When Panx1a function is lost, or both channels are under pharmacological blockade, seizures with ictal-like events and seizure-like locomotion are reduced in the presence of pentylenetetrazol. Transcriptome profiling by RNA-seq demonstrates a spectrum of distinct metabolic and cell signaling states which correlate with the loss of Panx1a. Furthermore, the pro- and anticonvulsant activities of both Panx1 channels affect ATP release and involve the purinergic receptor P2rx7. Our findings suggest a subfunctionalization of Panx1 enabling dual roles in seizures, providing a unique and comprehensive perspective to understanding seizure mechanisms in the context of this channel.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping