Penicillin- and barium-induced epileptiform bursting in hippocampal neurons: actions on Ca++ and K+ potentials.
Both barium (Ba++) and penicillin produce spontaneous epileptiform burst generation in hippocampal neurons in vitro. Recent investigations suggest that Ba++ acts by both adding to a calcium (Ca++)-mediated depolarization and reducing potassium (K+) conductance. In contrast, it has been proposed that penicillin produces burst generation by attenuating inhibitory postsynaptic potentials. However, some evidence suggests that penicillin may also directly alter intrinsic membrane properties. We therefore compared the actions of penicillin and Ba++ on three intrinsic Ca++- or K+-mediated membrane events, namely, CA++ spikes, Ca++-dependent anomalous rectification, and K+-dependent afterhyperpolarization. Ba++ augmented the Ca++ potentials and attenuated the K+-dependent afterhyperpolarization; penicillin had no demonstrable effect on these events. Ba++ produced rhythmical burst firing and oscillations of the membrane potentials, while penicillin caused sporadic burst generation followed by a longlasting afterhyperpolarization. Synchronized, orthodromically evoked burst firing occurred after exposure to penicillin but not to Ba++. Ba++ and penicillin are prototypes of agents which induce epileptogenesis in mammalian cortical neurons by two different but probably interrelated mechanisms. Ba++ causes burst generation by disrupting a delicate balance between depolarizing Ca++ potentials and repolarizing, hyperpolarizing K+ potentials. Penicillin does not affect Ca++- or K+-mediated membrane events; other data suggest that it produces burst generation in hippocampal pyramidal neurons by attenuating gamma-aminobutyric acid-mediated synaptic inhibition, which in turn ordinarily limits intrinsic bursting.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001464:Barium / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D004553:Electric Conductivity; D004594:Electrophysiology; D004827:Epilepsy / Q000503:physiopathology*; D006168:Guinea Pigs; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000502:physiology*; D010400:Penicillin G / Q000494:pharmacology*; D011188:Potassium / Q000502:physiology*
D001464:Barium; D010400:Penicillin G; D011188:Potassium; D002118:Calcium