The trapping block of NMDA receptor channels in acutely isolated rat hippocampal neurones

1. N-methyl-D-aspartate (NMDA) receptor responses were recorded from acutel y isolated rat hippocampal neurones using the whole-cell patch-clamp, techn ique. A rapid perfusion system was used to study the voltage-dependent bloc k of NMDA channels by Mg2+, amantadine (AM) and N-2-(adamantyl)-hexamethyle nimine (A-7). 2. Mg2+, AM and A-7-induced stationary blockade of NMDA channels increased with the blocker concentration but did not depend on the agonist (aspartate ; Asp) concentration. Blockade by AM and A-7, but not Mg2+, was weakly use dependent. 3. 'Hooked' tail currents were observed after coapplication of Asp and Mg2, AM or A-7. The hooked tail current kinetics, amplitude and carried charge indicated that Mg2+, AM and A-7 did not prevent closure and desensitizatio n of NMDA channels nor agonist dissociation. 4. Tail currents following Asp application in the absence and continuous pr esence of Mg2+, AM or A-7 had similar kinetics. 5. Application of multiple stationary and kinetic criteria to the Mg2+, AM and A-7 blockade led us to conclude that their effects on NMDA channels can be described in terms of a 'trapping' model, which is fully symmetrical wi th respect to the blocking transition. 6. In general, the apparent blocking/recovery kinetics predicted by the ful ly symmetrical trapping model differ significantly from the microscopic kin etics and depend on the rate of binding and unbinding of the blocker, the N MDA channel open probability and the rate of solution exchange.