Voltage-dependent block by strychnine of N-methyl-D-aspartic acid-activated cationic channels in rat cortical neurons in culture.
Single-channel currents were recorded by means of the patch clamp method in outside-out patches excised from rat cortical neurons in primary culture. The excitatory amino acid N-methyl-D-aspartic acid activated mainly 40-50 pS conductance channels. Channel opening durations were characterized by a series of rapid openings and closures induced by the presence of Mg2+ ions. This inhibitory effect was voltage dependent. Strychnine, the antagonist of the glycine-gated Cl- channels, blocks the N-methyl-D-aspartic acid-activated cationic channel in cultured rat cortical neurons. Strychnine action is voltage dependent and it is not counteracted by ethylenediaminetetraacetic acid, ruling out Mg2+ contamination of strychnine. It has been reported recently that glycine increases the rate of openings of N-methyl-D-aspartic acid-activated channels. This action is not affected by the presence of strychnine. Our results show that 1) Mg2+ and strychnine have an apparently similar intermediate blocking action on the NMDA-activated channels, 2) strychnine presumably acts as a sequential open channel blocker producing a different type of block compared with the one reported for Mg2+ ions, and 3) the lack of effect of strychnine on the glycine potentiation of the N-methyl-D-aspartic acid response indicates that this alkaloid does not competitively antagonize glycine but acts as an open channel blocker.
Bertolino
M
M
FIDIA-Georgetown Institute for the Neurosciences, Georgetown University Medical School, Washington, DC 20007.
Vicini
S
S
D000494:Allosteric Regulation; D000818:Animals; D002412:Cations; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects*; D004347:Drug Interactions; D005998:Glycine / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects*; D007608:Kainic Acid / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D016318:Quisqualic Acid; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D013331:Strychnine / Q000494:pharmacology*
D002412:Cations; D007473:Ion Channels; D010069:Oxadiazoles; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D016318:Quisqualic Acid; D013331:Strychnine; D008274:Magnesium; D007608:Kainic Acid; D005998:Glycine