Eosine-Induced Blockade ofN-Methyl-d-aspartate Channels in Acutely Isolated Rat Hippocampal Neurons
Abstract
Acutely isolated rat hippocampal neurons were voltage-clamped in the whole-cell configuration. The currents throughN-methyl-d-aspartate (NMDA) channels were elicited by fast application of aspartate in a Mg2+-free 3 μM glycine-containing solution. Eosine, known as a potent reversible inhibitor of the plasma membrane Ca2+ pump, proved to be able to induce a blockade of NMDA channels. The eosine-induced inhibition of NMDA-mediated currents enhanced with eosine concentration (IC50 = 248 μM) but did not depend on the membrane potential, agonist (aspartate) or coagonist (glycine) concentrations, pH, or the presence of spermine, ethanol, and the disulfide-reducing agents dithiothreitol and glutathione. Zn2+ inhibited NMDA channels with equal efficiency both in the presence and absence of eosine. These results suggest that eosine interacts with a new, previously unknown NMDA receptor regulatory site.
Footnotes
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Send reprint requests to: Dr. Alexander I. Sobolevsky, Institute of General Pathology and Pathophysiology, Baltiyskaya 8, 125315, Moscow, Russia. E-mail: rans{at}rans.msk.ru
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This work was supported by the Russian Fund for Fundamental Research and in abstract form was previously presented in the Society for Neuroscience 29th Annual Meeting (Soc Neurosci Abstr 25:200).
- Abbreviations:
- NMDA
- N-methyl-d-aspartate
- EOS
- eosine
- ASP
- aspartate
- GLY
- glycine
- DTT
- dithiothreitol
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- Received August 11, 1999.
- Accepted November 12, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
