Brain Research, 232 (1982) 41-56 41 Elsevier Biomedical Press MEMBRANE DEPOLARIZATION AND PROLONGATION OF CALCIUM- DEPENDENT ACTION POTENTIALS OF MOUSE NEURONS IN CELL CULTURE BY TWO CONVULSANTS: BICUCULLINE AND PENICILLIN ERIC J. HEYER*, LINDA M. NOWAK and ROBERT L. MACDONALD** Department of Neurology and (L.M.N.) NeurosciencesProgram, University of Michigan Medical Center, NeuroscienceLaboratory BMlding, 1103 East Huron, Ann Arbor, MI 48109 (U.S.A.) (Accepted June 25th, 1981) Key words: bicuculline -- penicillin -- neurons -- cell culture -- calcium action potentials SUM MARY The convuisant compounds bicuculline (BICUC) and penicillin (PCN) are antagonists of GABA-mediated synaptic inhibition. In addition, we have shown that BICUC and PCN produced membrane depolarization of mouse spinal cord neurons in primary dissociated cell culture by blocking a potassium conductance, a non- synaptic direct effect. Both compounds also prolonged calcium-dependent action potentials of mouse dorsal root ganglion and spinal cord neurons in cell culture. Thus, BICUC and PCN had both synaptic and non-synaptic actions. The possibility that both synaptic and non-synaptic actions of BICUC and PCN are involved in their convulsant mechanism of action is discussed. INTRODUCTION Bicuculline (BICUC) and penicillin (PCN) produce generalized seizures when administered systemically24,41,51. Topical application of convulsant compounds to cerebral ccrtex or hippocampus leads to development of epileptiform discharges or 'spikes' recorded with surface electroencephalographie (EEG) electrodes 15,18,82. Such convulsant-induced spikes are similar in form to those recorded in the interictal EEG of patients with epilepsy. Intracellular recordings obtained from neurons within convulsant-induced seizure foci demonstrated large depolarizations evoking volleys of action potentials which occurted randomly and were co~related with the occurrence of * Present address: Department of Neurology, Mt. Sinai School of Medicine, New York, NY 10029, U.S.A. ** To whom correspondence should be addressed. 0006-8993/82/0000-0000/$02.75 © Elsevier Biomedical Press