CA2-DEPENDENT NON-NMDA RECEPTOR-MEDIATED SYNAPTIC CURRENTS IN ISCHEMIC CA1 HIPPOCAMPAL-NEURONS()

1. The changes in excitatory postsynaptic currents (EPSCs) after trans ient cerebral ischemia were studied using whole-cell recording from CA l pyramidal neurons in gerbils. In 64% (18 of 28) neurons recorded 1.5 -3 days after ischemia, EPSCs showed a markedly slowed time course tha t was never seen in normal control neurons. 2. The slow EPSCs were not affected by an N-methyl-D-aspartate (NMDA) receptor antagonist [DL-2- aminophosphonovalerate (APV); 100 mu M] but were abolished by a non-NM DA receptor antagonist [6-cyano-7-nitroquinoxaline-2,3-dione (CNQX); 1 0 mu M], indicating that the slow EPSCs were mostly composed of non-NM DA current. 3. The slow non-NMDA EPSCs had rise times ranging from 1.2 to 7.3 ms and decay time constants between 11.5 and 56.3 ms. In norma l neurons the rise time of the non-NMDA component of EPSCs ranged from 1.6 to 7.5 ms and the decay time constants ranged from 4.9 to 27.3 ms . 4. The reversal potential of the slow EPSCs in ischemic neurons was not changed by replacing 50% of the NaCl in the external solution with sodium isethionate. Bath application of cetamido-4'-isothiocyanatosti lbene-2,2'-disulfonic acid (SITS; 100 mu M) had no effect on the slow EPSCs. Therefore Cl- current is not responsible for the slow EPSCs. 5. When external Ca2+ concentration was reduced to half of control, the decay time constant of the slow EPSCs decreased to 50 +/- 25%, mean +/ - SD. In addition, bath application of a cell-permeable Ca2+ chelator, 2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetyl, tetraacetoxymethyl ester( BAPTA-AM), reduced the decay time constant.