Effects of NMDA antagonists on picrotoxin-, low Mg2+- and low Ca2+-induced epileptogenesis and on evoked changes in extracellular Na+ and Ca2+ concentrations in rat hippocampal slices.
The anticonvulsant properties of ketamine and 2-APV were compared on 3 types of convulsant activity in hippocampal area CA1: the 'picrotoxin-epilepsy,' the 'low magnesium epilepsy' and the 'low calcium epilepsy.' In particular the spontaneous activity, the synaptically evoked responses and the changes in [Ca2+]0 were examined, since in many cases of epilepsy, Ca2+ uptake into cells is enhanced. In normal medium, ketamine and 2-APV have nearly no effect on stimulus evoked decreases in [Ca2+]0, although they clearly depress NMDA-induced ionic changes. However, ketamine and 2-APV prevent to some extent the augmentation of stimulus-induced changes in [Ca2+]0, observed after treating slices with picrotoxin or Mg2+-free medium. This extra Ca2+ uptake is probably mediated by NMDA operated channels. Our findings also show that ketamine, like 2-APV, has a stronger anticonvulsant effect on the low Mg-than on the picrotoxin-induced epileptiform activity. Responses to iontophoretically applied NMDA are facilitated in the 'low calcium epilepsy' and can be selectively blocked by ketamine. Spontaneous epileptiform activity occurring in low calcium can be blocked by ketamine only when some synaptic transmission is still present.
Köhr
G
G
Institut für normale und pathologische Physiologie, Universitt Köln, Cologne, F.R.G.
Heinemann
U
U
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000502:physiology*; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology*; D008274:Magnesium / Q000502:physiology*; D010852:Picrotoxin; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000502:physiology*
D015763:2-Amino-5-phosphonovalerate; D002118:Calcium; D007649:Ketamine; D008274:Magnesium; D010852:Picrotoxin; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter