Two-component blocking kinetics of open NMDA channels by organic cations.

NMDA receptor channel responses were recorded from acutely isolated rat hippocampal neurons, using whole-cell patch-clamp techniques. In the continuous presence of aspartate, tetraethylammonium, tetrabutylammonium, 1-amino-3-propyl-adamantane and 9-aminoacridine caused changes in the current through NMDA channels, which were described by two-exponential functions. It was established that depending on the behavior of the amplitude of the fast component for the recovery kinetics, the blocker action can be assigned to one of five types described by the simplest models. The effects of tetraethylammonium, tetrabutylammonium and 1-amino-3-propyl-adamantane were well described by these models. Using 9-aminoacridine as an example, it was shown that the simplest models cannot describe all possible types of the blocker-channel interaction. In such cases, the method of the simplest models combination can be used. The application of the simplest kinetic models analysis allowed to make the following conclusions: at least two molecules of 1-amino-3-propyl-adamantane or 9-aminoacridine can simultaneously bind to the open channel and block it; the occupation of 9-aminoacridine blocking sites in the channel can proceed in at least two different ways; the binding of tetrabutylammonium and 9-aminoacridine prevented the closure of the activation and/or desensitization gates of the channel, while that of tetraethylammonium did not.