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GABA-dependent generation of ectopic action potentials in the rat hippocampus
M Avoli1, M Methot, H Kawasaki
1Cell Biology of Excitable Tissue Research Group, Montreal Neurological Institute and Departments of Neurology & Neurosurgery, and of Physiology, McGill University, Montreal, QC, H3A 2B4, Canada. cyav@musica.mcgill.ca
The European Journal of Neuroscience
|October 10, 1998
Summary
In a rat hippocampus model, variable amplitude action potentials in CA3 pyramidal cells originate from axon terminals, driven by GABA-A receptors and elevated potassium levels. These findings shed light on epilepsy mechanisms.
Area of Science:
- Neuroscience
- Epilepsy Research
- Cellular Electrophysiology
Background:
- 4-aminopyridine (4AP) application in rat hippocampus slices induces interictal epileptiform discharges.
- These discharges are accompanied by synchronous GABA-mediated potentials, characterized by hyperpolarization and long-lasting depolarization (LLD).
- Variable amplitude action potentials were observed in CA3 pyramidal cells during these events.
Purpose of the Study:
- To investigate the origin and underlying mechanisms of variable amplitude action potentials in CA3 pyramidal cells during 4AP-induced epileptiform activity.
- To determine the role of GABAergic and glutamatergic neurotransmission in generating these action potentials.
- To elucidate the contribution of axon terminal excitability to ectopic action potential generation in epilepsy models.
Main Methods:
- Intracellular recordings from CA3 pyramidal cells in rat hippocampus slice preparations.
- Application of 4-aminopyridine (4AP) to induce epileptiform activity.
- Pharmacological manipulations using excitatory amino acid receptor antagonists, GABAB antagonist CGP-35348, and GABAA antagonist bicuculline methiodide (BMI).
- Localized application of BMI and tetrodotoxin (TTX) to specific hippocampal strata (CA1 and CA3).
Main Results:
- Interictal discharges were blocked by excitatory amino acid receptor antagonists.
- GABA-mediated potentials and variable amplitude action potentials persisted after glutamate receptor blockade.
- Variable amplitude action potentials were abolished by GABAA antagonist bicuculline methiodide (BMI) but not by GABAB antagonist CGP-35348.
- Localized application of BMI or TTX to the CA1 stratum radiatum blocked these action potentials, indicating an origin at or near axon terminals.
- These effects were not observed when BMI or TTX were applied to the CA3 stratum radiatum.
Conclusions:
- Action potentials of variable amplitude in CA3 pyramidal cells during 4AP application are TTX-sensitive ectopic events generated at or near Schaffer collateral terminals.
- These ectopic action potentials are mediated by a GABAA-dependent mechanism, suggesting increased axon terminal excitability.
- The findings propose that elevated extracellular potassium ([K+]o) associated with synchronous GABA-mediated potentials contributes to the hyperexcitability of axon terminals.