Ketamine Inhibition of Pentameric Ligand-Gated Ion Channels - Insights from Molecular Dynamics Simulations

Abstract

The anesthetic ketamine is well known as a non-competitive antagonist of N-methyl-D-aspartate receptors (NMDARs). However, not all the clinical effects of ketamine can be fully explained by its inhibition of NMDARs. An alternative mode of ketamine action is through inhibition of pentameric ligand-gated ion channels (pLGICs), such as nicotinic acetylcholine receptors. Ketamine inhibits the bacterial pLGIC from Gloeobacter violaceus (GLIC) and the ketamine-GLIC co-crystallized structure was determined previously.