4-aminopyridine-induced epileptiform activity and a GABA-mediated long-lasting depolarization in the rat hippocampus.
The effects of topical application of microdrops containing 4-aminopyridine (4-AP) on properties of CA1 neurons were examined in the hippocampal slice preparation. 4-AP triggered repetitive large (4-10 mV) hyperpolarizing potentials (HPs) having a short rise time and slow (3-4 s) decay. There was a marked decrease in input resistance during the HPs. The HPs are likely to be caused by an increase in potassium conductance; their reversal potential was 15-20 mV negative to rest, the reversal potential shifted in the depolarizing direction when the slice was bathed in high potassium medium, and it was the same with KCl or potassium acetate recording electrodes. The HPs were not generated by release of neurotransmitter substances from terminals of extrinsic afferents since they were present in slices taken from deafferented hippocampus but they were blocked by tetrodotoxin (TTX) or Cd and Mn, indicating that they are synaptic potentials of local origin. HPs were still present when Ca-dependent K currents were blocked by acetylcholine and noradrenaline. Three of 56 cells recorded in the hippocampus could be classified as interneurons. They emitted high frequency trains of action potentials in response to 4-AP, at a rate corresponding to the HPs recorded in all other neurons. It is suggested that 4-AP excites a specific type of interneuron which in turn generates large K-mediated inhibitory postsynaptic potentials in the pyramidal neurons of CA1 region of the hippocampus.