Inhibitory mechanisms in epileptiform activity induced by low magnesium.
In rat hippocampal slices epileptiform activity was induced by superfusion with Mg(2+)-free artificial cerebrospinal fluid (ACSF). Paroxysmal depolarization shifts (PDS) were evoked by electrical stimulation of Schaffer collaterals. To investigate the afterpotentials that follow PDS, intracellular recordings were made from CA1 pyramidal cells. The experiments revealed that several components are engaged in the generation of PDS afterpotentials in Mg(2+)-free ACSF. A long lasting component which determined the overall duration of the PDS afterhyperpolarization was blocked by intracellular application of ethylenebis(oxonitrilo)-tetraacetate (EGTA); concomitantly, the afterhyperpolarizations following depolarizing current injections were blocked. This indicated that the long lasting component was due to a slow Ca(2+)-activated K+ current. The block of Ca(2+)-activated K+ current uncovered a depolarizing PDS afterpotential with an N-shaped voltage dependence, suggesting that this depolarizing afterpotential component may be due to an N-methyl D-aspartate (NMDA) conductance. Intracellular injection of Cl- revealed that the PDS were followed by Cl- currents lasting about 500 ms. This component could be blocked by application of bicuculline suggesting that it is due to a synaptically GABA-mediated (i.e. gamma-aminobutyric acid) Cl- current. A comparison of PDS afterpotentials in Mg(2+)-free ACSF and those in other models of epileptiform activity suggests that similar sequences of inhibitory components are activated in spite of different pharmacological alterations of membrane conductances which induce the epileptiform discharges.
Westerhoff
C H
CH
Neurologische Klinik der Heinrich-Heine-Universität, Düsseldorf, Germany.
Domann
R
R
Witte
O W
OW
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D018118:Chloride Channels / Q000502:physiology; D002712:Chlorides / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004553:Electric Conductivity; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008274:Magnesium / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials; D016202:N-Methylaspartate / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D018118:Chloride Channels; D002712:Chlorides; D015221:Potassium Channels; D004533:Egtazic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D008274:Magnesium; D002118:Calcium; D001640:Bicuculline