ELSEVIER Neuroscience Letters 176 (1994) 71-74 NEUROSCIENCE LHIERS Inhibitory mechanisms terminating paroxysmal depolarization shifts in hippocampal neurons of rats Roland Domann, Christian H.A. Westerhoff, Otto W. Witte* Neurologische Klinik der Heinrich-Heine-Universitiit, Moorenstr. 5. D-40225 Dusseldorf, FRG Received 14 April 1994; Revised version received24 May 1994; Accepted 25 May 1994 Abstract The mechanisms responsible for the termination of paroxysmal depolarization shifts (PDS) were studied with intracellular recordings on CA1 neurons of rat hippocampal slices. Epileptiform activity was induced by application of penicillin, bicuculline or Mg-free artificial cerebrospinal fluid (ACSF). PDS in penicillin-containing and Mg-free ACSF were markedly prolonged when GABAA-dependent IPSPs were blocked by bicuculline. PDS in bicuculline-containing ACSF were furthermore prolonged after block of potential dependent K ÷ conductances by TEA. TEA also exerled some effect on PDS induced by penicillin containing or Mg-free ACSF. Block of GABAB-dependent IPSPs or Ca2+-dependent K ÷ currents did not affect PDS duration in any of the three models. It is concluded that PDS termination is due to active inhibitory processes which comprise different components. If one of these components is blocked another inhibitory component governs PDS repolarization resulting in PDS with a slightly different duration but otherwise unchanged features. Key words: Paroxysmal depolarization shift; Afterpotential; Hippocarnpus; Experimental epilepsy; Rat; Penicillin; Bicuculline; GABA The characteristic feature of interictal epileptic dis- charges are short spikes or sharp waves in the EEG. The intracellular correlate of these epileptic events are parox- ysmal depolarization shifts (PDS) [9]. Experimentally, such epileptic phenomena can be introduced by drugs which cause changes of intrinsic or synaptic membrane currents [4]. Thus penicillin or bicuculline reduce inhib- itory GABAA currents [8] while in Mg2÷-free solution excitatory postsynaptic potentials are increased [12]. In spite of these differences, the PDS look very much alike: they begin with a rapid series of action potentials fol- lowed by a more or less pronounced plateau phase which passes over into a rapid re- and hyperpolarization [9]. The question arises which of the phenomena are specific for a certain model of epilepsy and which represent gen- eral features of the brain and are thus also of potential *Corresponding author. Fax: (49) 211-342 229. 0304-3940/94/$7.00© 1994 Elsevier ScienceIreland Ltd. All rights reserved SSDI 0304-3940(94)00416-8 relevance for the explanation of epileptic processes in the human brain. In the different models mechanisms exist which termi- nate the PDS and thereby prevent the transition to ictal discharges [16]. In accordance with this, the durations of PDS increase before ictal discharges occur [10]. In the present study we therefore investigated which mecha- nisms terminate the PDS in different acute models of epilepsy. The experiments were performed on hippocampal slices of Wistar rats (300 g body weight). Under ether anesthesia, the rats were decapitated, the hippocampi were dissected free and cut into transverse slices of 400 Bm. The slices were equilibrated with standard artificial cerebrospinal fluid (standard ACSF, containing: 124 mM NaC1, 26 mM NaHCO3, 5 mM KCI, 2 mM CaCI2, 2 rnM MgSO4, 1.25 mM NaH2PO4, 10 mM glucose, equilibrated with 95% 02/5% CO2, pH 7.4) for at least 1 h. Epileptiform activity was induced by adding 3.4 mM penicillin (penicillin ACSF) or 100 BM bicuculline