Cholinergic direct inhibition of N-methyl-D aspartate receptor-mediated currents in the rat neocortex.

Synapse
Jorge Flores-HernandezMarco Atzori

Abstract

Acetylcholine (ACh) and N-methyl-D aspartate receptors (NMDARs) interact in the regulation of multiple important brain functions. NMDAR activation is indirectly modulated by ACh through the activation of muscarinic or nicotinic receptors. Scant information is available on whether ACh directly interacts with the NMDAR. By using a cortical brain slice preparation we found that the application of ACh and of other drugs acting on muscarinic or nicotinic receptors induces an acute and reversible reduction of NMDAR-mediated currents (I(NMDA)), ranging from 20 to 90% of the control amplitude. The reduction displayed similar features in synaptic I(NMDA) in brain slices, as well as in currents evoked by NMDA application in brain slices or from acutely dissociated cortical cells, demonstrating its postsynaptic nature. The cholinergic inhibition of I(NMDA) displayed an onset-offset rate in the order of a second, and was resistant to the presence of the muscarinic antagonist atropine (10 microM) in the extracellular solution, and of G-protein blocker GDP(beta)S (500 microM) and activator GTP(gamma)S (400 microM) in the intracellular solution, indicating that it was not G-protein dependent. Recording at depolarized or hyperpolarized holding...Continue Reading

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Citations

May 16, 2015·Neuroscience and Biobehavioral Reviews·Nikolaos C Aggelopoulos
Apr 28, 2010·Expert Review of Neurotherapeutics·Tomasz Sobow
Mar 7, 2021·International Journal of Molecular Sciences·Yu-Jung ChengHsien-Yuan Lane

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