AFTERPOTENTIALS FOLLOWING PENICILLIN-INDUCED PAROXYSMAL DEPOLARIZATIONS IN RAT HIPPOCAMPAL CA1 PYRAMIDAL CELLS-INVITRO

Epileptic discharges were induced by superfusion of rat hippocampal slices with penicillin. Under these conditions the neurons generated paroxysmal depolarization shifts (PDS) after electrical stimulation of Schaffer collaterals. The PDS were followed by large afterhyperpolarizations lasting about 2 s. The mechanisms causing these afterhyperpolarizations were studied in CA1 pyramidal cells. A late component of the afterhyperpolarizations, which determined their overall duration, was blocked by intracellular application of EGTA and reduced by superfusion with 8-Br-cAMP. In the same neurons these drugs had a comparable effect on after-hyperpolarizations following depolarizing current injections; it was therefore concluded that the late component of the PDS afterhyperpolarizations was caused by a slow Ca2+-activated K+ current. An initial fast component of PDS afterhyperpolarizations, which peaked about 60 ms after PDS onset, was reduced by EGTA but not affected by 8-Br-cAMP suggesting that the fast Ca2+-activated K+ current also contributed to the PDS afterhyperpolarizations. Superfusion of the slice with the gamma-aminobutyric acid B receptor (GABA(B)) antagonists phaclofen or 5-aminovalerate reduced the amplitude of the afterhyperpolarizations during the first 1000 ms but did not affect the late Ca2+-dependent component, indicating that a GABA(B)-mediated K+ inhibitory postsynaptic potential (IPSP) contributed to the PDS afterhyperpolarization. Intracellular injection of Cl- revealed that an early part of the afterhyperpolarizations lasting about 500 ms was Cl--dependent. This component was blocked by superfusion of the slices with bicuculline, suggesting that a GABA(A)-mediated Cl- IPSP contributed to the PDS afterhyperpolarization. The experiments show that different synaptic and intrinsic components with different time courses participate in the generation of PDS afterpotentials.