Abstract
Neurones isolated from the CA1 region of rat hippocampal slices by the “vibrodissociation” method were voltage-clamped in the whole-cell configuration. The currents through N-methyl- d-aspartate (NMDA) channels were recorded in response to the rapid application (solution exchange time <30 msec) of 100 μM aspartate (ASP) in a Mg 2+-free solution in the presence of 3 μM glycine. When added to the ASP solution, bepridil (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 (IC 50) for the stationary current was 14.01 ± 0.17 μM ( n = 10). The blocking and unblocking time constants were 7.4 ± 0.3 × 10 3/M/sec and 0.12 ± 0.02/sec, respectively. Membrane hyperpolarization enhanced the BPD block. The equilibrium dissociation constant behaved as an exponential function of the membrane potential and increased e-fold every 37 mV. © 1997 Elsevier Science Ltd. All rights reserved.
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