The actions of L-687,384, a sigma receptor ligand, on NMDA-induced currents in cultured rat hippocampal pyramidal neurons.
The actions of the sigma receptor ligand L-687,384 were studied on N-methyl-D-aspartate (NMDA)-induced currents recorded from outside-out patches obtained from cultured rat hippocampal pyramidal neurons and on NMDA-evoked rises in [Ca2+]i in the same preparation. L-687,384 did not change the magnitudes of unitary NMDA currents or frequency of channel-openings but diminished channel-open probability by decreasing mean open time. This action was consistent with a voltage-dependent open-channel block of the NMDA channel by L-687,384 with a blocking rate constant of 5.9 x 10(6) M-1 s-1 at -80 mV. L-687,384 also reduced NMDA-evoked rises in [Ca2+]i in Fura-2-loaded neurons with an apparent IC50 value of 49 +/- 8 microM. The results demonstrate that L-687,384 acts as an antagonist at the NMDA receptor-channel complex.
McLarnon
J
J
Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada.
Sawyer
D
D
Church
J
J
D000818:Animals; D002478:Cells, Cultured; D003592:Cytophotometry; D016257:Fura-2; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects*; D016202:N-Methylaspartate / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D017480:Receptors, sigma / Q000187:drug effects*
D007473:Ion Channels; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D017480:Receptors, sigma; D016202:N-Methylaspartate; C090669:L 687384; D016257:Fura-2