2 BLOCKING SITES OF AMINO-ADAMANTANE DERIVATIVES IN OPEN N-METHYL-D-ASPARTATE CHANNELS

Using whole-cell patch-clamp techniques, we studied the blockade of op en N-methyl-D-aspartate (NMDA) channels by amino-adamantane derivative s (AADs) in rat hippocampal neurons acutely isolated by the vibrodisso ciation method. The rapid concentration-jump technique was used to rep lace superfusion solutions. A kinetic analysis of the interaction of A AD with open NMDA channels revealed fast and slow components of their blockade and recovery. Mathematical modeling showed that these kinetic components are evidence for two distinct blocking sites of AADs in op en NMDA channels. A comparative analysis of different simplest models led us to conclude that these AAD blocking sites can be simultaneously occupied by two blocker molecules. The voltage dependence of the AAD block suggested that both sites were located deep in the channel pore.