Chapter 5 : Glutamate-Activated Channels

Abstract:

Ligand-gated ion channels (LGICs) are a major class of ion channels. Postsynaptic LGICs generate electrical signals in response to specific chemical neurotransmitters such as acetylcholine, glutamate, glycine, or γ-aminobutyric acid. Understanding the polymorphism of the genes encoding the GluRs in particular will increase one's understanding of the role of these receptors in neurogenetic variations. Animal glutamate receptors possess both metabotropic glutamate receptors (mGluRs) and ionotropic glutamate receptors (iGluRs). The iGluRs and mGluRs are classified into subgroups based on their sequence homology, agonist pharmacology, and intracellular transduction mechanisms. The structural and sequence similarity of the different domains of GluRs to proteins from different types of organisms gives rise to some interesting implications in the evolutionary relationship between prokaryotes and eukaryotes. The iGluRs are classified as nmethyl-D-aspartic acid (NMDA) receptors or non-NMDA receptors, which include kainate (KAI) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. The first prokaryotic glutamate receptors to be discovered was GluR0 from Synechocystis sp. strain PCC 6803. An interesting observation was made based on scores of the similarity of profiles of the P-loop and M2 helix. Plant glutamate receptors (GLRs) were first identified in Arabidopsis thaliana. The sequencing of the complete genome of A. thaliana revealed the existence of not 1 but 20 genes that encoded putative GLRs. A famous quote of Theodosius Dobzhansky, “Nothing in biology makes sense, except in the light of evolution,” emphasizes the importance of evolutionary studies in biology. Evolutionary inferences essentially rely on diversity among organisms, where the differences are accumulated randomly from some common ancestor.