Deactivation of N-methyl-D-aspartate (NMDA) channels after brief agonist ex
posure determines the duration of their synaptic activation during excitato
ry neurotransmission. We performed patch-clamp recordings of L-glutamate re
sponses from human embryonic kidney tumoral cells (HEK293) expressing NR1 s
ubunit variants lacking exon 5 together with the NR2B subunit. These respon
ses had deactivation components that lasted several seconds. The presence o
f exon 5 or spermine greatly accelerated deactivation of L-glutamate respon
ses through alterations in desensitization. These effects were also observe
d at positive holding potentials and in the presence of physiological Mg2+.
Thus NR1 splicing and polyamines may have profound effects on the kinetics
of NMDA receptor-mediated synaptic transmission.