The polyamine diaminodecane (DA-10) produces a voltage-dependent flickery block of single NMDA receptor channels.
Receptor binding assays have shown that diaminodecane (DA-10) reduced binding of open channel blockers to the N-methyl-D-aspartate (NMDA) subtype of postsynaptic glutamate receptor through an interaction with the polyamine regulatory site. Because the action of DA-10 was opposite to that of the polyamine agonist spermine and was reversed by polyamine antagonists, DA-10 has been classified as an inverse agonist at the polyamine site. Using whole-cell voltage-clamp and single-channel recordings from cultured rat cortical neurons, we show that at negative holding potentials DA-10 (1-300 microM) reduced NMDA receptor whole cell current (IC50 = 34 microM) and produced a flickery block of NMDA single-channel currents. The flickery block of NMDA single channels was voltage-dependent and not reversed by the polyamine antagonist diethylenetriamine (DET). Potential mechanisms for the flickery block of NMDA single channel currents are discussed.
D000818:Animals; D003959:Diamines / Q000494:pharmacology*; D005260:Female; D007473:Ion Channels / Q000187:drug effects*; D007700:Kinetics; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D011073:Polyamines / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D013096:Spermine / Q000494:pharmacology
C065351:1,10-diaminodecane; D003959:Diamines; D007473:Ion Channels; D011073:Polyamines; D016194:Receptors, N-Methyl-D-Aspartate; C005391:diethylenetriamine; D013096:Spermine; D016202:N-Methylaspartate