Eosine-induced blockade of N-methyl-D-aspartate channels in acutely isolated rat hippocampal neurons

• Published in: Molecular pharmacology Vol. 57; no. 2; pp. 334 - 341
• Main Authors: Sobolevsky, A I, Yelshansky, M V, Khodorov, B I
• Format: Journal Article
• Language: English
• Published: United States 01.02.2000
• Subjects: Animals; Eosine Yellowish-(YS) - pharmacology; Hippocampus - drug effects; Hippocampus - metabolism; In Vitro Techniques; Neurons - drug effects; Neurons - metabolism; Rats; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors
• ISSN: 0026-895X; 1521-0111

Acutely isolated rat hippocampal neurons were voltage-clamped in the whole-cell configuration. The currents through N-methyl-D-aspartate (NMDA) channels were elicited by fast application of aspartate in a Mg(2+)-free 3 microM glycine-containing solution. Eosine, known as a potent reversible inhibitor of the plasma membrane Ca(2+) pump, proved to be able to induce a blockade of NMDA channels. The eosine-induced inhibition of NMDA-mediated currents enhanced with eosine concentration (IC(50) = 248 microM) 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. Zn(2+) 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.