The structural patterns of the potentiation and the blockade of inhibitory cys-loop receptors through the transmembrane domain

Abstract

Anion-conducting cys-loop receptors activated by -aminobutyric acid (GABAАRs) and glycine (GlyRs) have inhibitory activity in the brain and spinal cord. GABAАRs and GlyRs are targets for various substances that potentiate or inhibit the receptor functions. Many of these substances are clinically significant agents to treat neurological and psychiatric conditions. The review covers both our results and literature data on electrophysiology, mutations, and biochemistry of non-competitive antagonists, general anesthetics, barbiturates, and fenamates modulating GABAАRs and GlyRs. We focused on our own molecular modeling to determine the sites and the characteristics of binding of these substances to the GABAАR and GlyR transmembrane domain. With the structural patterns of the binding, we have identified possible molecular mechanisms of action for these substances.