BEPRIDIL-INDUCED BLOCKADE OF NMDA CHANNELS IN RAT HIPPOCAMPAL-NEURONS

Neurones isolated from the CA1 region of rat hippocampal slices by the ''vibrodissociation'' method were voltage-clamped in the whole-cell c onfiguration. The currents through N-methyl-D-aspartate (NMDA) channel s were recorded in response to the rapid application (solution exchang e time < 30 msec) of 100 mu M aspartate (ASP) in a Mg2+-free solution in the presence of 3 mu M glycine. When added to the ASP solution, bep ridil (BPD) caused a concentration-dependent decrease in both peak and stationary currents due to an uncompetitive open-channel blockade of NMDA channels. At -100 mV, the half-blocking concentration (IC50) for the stationary current was 14.01 +/- 0.17 mu M (n = 10). The blocking and unblocking time constants were 7.4 +/- 0.3 x 10(3)/M/sec and 0.12 +/- 0.02/sec, respectively. Membrane hyperpolarization enhanced the BP D block. The equilibrium dissociation constant behaved as an exponenti al function of the membrane potential and increased e-fold every 37 mV . (C) 1997 Elsevier Science Ltd.