Interactions of dextromethorphan with theN-methyl-d-aspartate receptor-channel complex: single channel recordings
| Autor: | Dale Sawyer, James G. McLarnon, John Church |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Hippocampus
Hippocampal formation Pharmacology Dextromethorphan Receptors N-Methyl-D-Aspartate Ion Channels Reaction rate constant medicine Animals Fluorometry Molecular Biology Neurons Chemistry General Neuroscience Glutamate receptor Conductance Rats Electrophysiology Dizocilpine Kinetics Biophysics NMDA receptor Neurology (clinical) Developmental Biology medicine.drug |
| Zdroj: | Brain Research. 666:189-194 |
| ISSN: | 0006-8993 |
| Popis: | The actions of dextromethorphan (DXM) on the 50 pS conductance state of the N-methyl- d -aspartate (NMDA) receptor-operated channel were studied using outside-out patches obtained from cultured rat hippocampal pyramidal neurons. DXM (5–50 μM) had no effect on the amplitudes of unitary currents but caused concentration-dependent reductions in channel mean open times and the frequency of channel openings. Channel open probability was reduced in a concentration-dependent manner by DXM and was one-half of the control value at a DXM concentration of 6 μM, with the patch potential held at −60 mV. An IC 50 value of 4 μM was obtained for the reduction by DXM of NMDA-evoked rises in [Ca 2+ ] i in cultured rat hippocampal pyramidal neurons loaded with Fura-2. The results were consistent with drug block of the open NMDA channel with an onward (blocking) rate constant of 7.7 × 10 6 M −1 · s −1 (at −60 mV). The estimated unblocking rate constant was about 10 s −1 , a value considerably higher compared to the off-rate constant found for dizocilpine block of the NMDA channel. |
| Databáze: | OpenAIRE |
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