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Epileptiform activity in hippocampal slice cultures exposed chronically to bicuculline: increased gap junctional
Marina Samoilova1, Jianxue Li, Marc R Pelletier
1Bloorview Epilepsy Research Laboratory, Division of Cellular and Molecular Biology, Toronto Western Research Institute, Toronto, Ontario, Canada.
Journal of Neurochemistry
|July 16, 2003
Summary
Blocking GABA receptors with bicuculline methiodide (BMI) increased gap junction proteins (connexin 43 and 32) and enhanced neuronal communication. This led to increased epileptiform discharges, suggesting a role for gap junctions in epilepsy.
Area of Science:
- Neuroscience
- Cell Biology
- Epilepsy Research
Background:
- GABA receptors are crucial for inhibitory neurotransmission in the brain.
- Gap junctions facilitate direct cell-to-cell communication.
- Epileptiform discharges are characteristic of seizure activity.
Purpose of the Study:
- To investigate the effect of blocking type-A GABA receptors on gap junction expression and function.
- To determine the role of gap junctional communication in BMI-induced epileptiform activity.
Main Methods:
- Cultured hippocampal slices were exposed to bicuculline methiodide (BMI).
- RNase protection assays and western blotting were used to measure connexin mRNA and protein levels.
- Fluorescence recovery after photobleaching assessed gap junctional coupling.
- Extracellular recordings measured epileptiform discharges.
Main Results:
- BMI increased connexin 43 (Cx43) and connexin 32 (Cx32) mRNA and protein levels.
- Gap junctional coupling and c-fos expression were significantly increased by BMI.
- BMI-exposed cultures exhibited increased frequency and duration of epileptiform discharges.
- Carbenoxolone, a gap junction blocker, inhibited these epileptiform discharges.
Conclusions:
- Increased gap junction expression and function correlate with enhanced epileptiform activity.
- Enhanced gap junctional communication plays a role in the epileptogenic process.
- Targeting gap junctions may offer a therapeutic strategy for epilepsy.