Effect of a non-hydrolyzable analog of diadenosine polyphosphates on NMDA-mediated currents in isolated pyramidal neurons of the rat hippocampus

Abstract

Using a patch-clamp technique under voltage clamp conditions, we studied the effect of a non-hydrolyzable analog of diadenosine polyphosphates (AppCH 2 ppAs) on chemoactivated transmembrane currents through NMDA channels (NMDA currents) in isolated pyramidal neurons of the rat hippocampal СА3 zone. In 55.7% of the cases, AppCH 2 ppAs caused an increase in the peak amplitude of the currents induced by application of aspartate. In 39.5% of the cases, the agent exerted no effect, while in 4.8% these currents were suppressed. When studying the pharmacological effect of an increase in the amplitude of NMDA currents, we found that potentiation of these currents is mediated, first of all, by activation of Р 2 purinoceptors and is prevented by a blocker of tyrosine kinases, genistein. Receptor-channel NMDA complexes, due to their ability to be blocked by divalent cations, also contribute to the above effect of AppCH 2 ppA. Based on the data obtained, we conclude that AppCH 2 ppA influences NMDA receptors via activation of the P 2 receptors and subsequent activation of tyrosine kinases; this leads to the modification of receptor-channel NMDA complexes and to the removal of their tonic blocking by zinc ions.