The channel-associated protein PSD-95 functionally modulates NMDA receptor channels, interacting,vith the channels via PDZ domain of PSD-95, PSD-95 also interacts with guanylate kinase-associated protein (GKAP) through the guanylate kinase-like domain of PSD-95. Here we report that GKAP markedly potentiates the channel activity of the receptor-PSD-95 complex. However, GKAP had no effect on basic properties of the channels nor on PSD-95-induced changes in channel properties. Thus, GKAP affects the channel activity of the NMDA receptor via PSD-95 quantitatively,,which may make signal transmission more efficient at postsynaptic sites. (C) 1999 Federation of European Biochemical Societies.