Dynorphin A (1-10) binds in the transmembrane domain of the κ-receptor. The non-opioid actions of various forms of Dynorphin A (DynA) are examined on N-methyl-D-aspartate (NMDA) receptor channels in isolated rat trigeminal neurons using the whole-cell patch recording technique. All the dynorphins tested blocked NMDA-activated currents. The blocking actions are voltage-independent. The IC
50
is 42.0 μM for DynA(1-10). To determine if shorter dynorphins have the similar blocking property, we examined the action of DynA(1-10) at different membrane potentials. DynA(1-10) blocks I
NMDA
to a similar extent as the membrane potentials changed from -80 to +60 mV. Thus, despite a 160-fold difference in the apparent affinities, DynA(1-32) and DynA(1-10) both exert voltage-independent actions on NMDA receptors.