title: Advances in the pharmacology of lGICs auxiliary subunits.
abstract: Ligand-gated ion channels (LGICs) are cell surface integral proteins that mediate the fast neurotransmission in the nervous system. LGICs require auxiliary subunits for their trafficking, assembly and pharmacological modulation. Auxiliary subunits do not form functional homomeric receptors, but are reported to assemble with the principal subunits in order to modulate their pharmacological profiles. For example, nACh receptors are built at least by co-assemble of α and β subunits, and the neuronal auxiliary subunits β3 and α5 and muscle type β, δ, γ, and ϵ determine the agonist affinity of these receptors. Serotonergic 5-HT3B, 5-HT3C, 5-HT3D and 5-HT3E are reported to assemble with the 5-HT3A subunit to modulate its pharmacological profile. Functional studies evaluating the role of γ2 and δ auxiliary subunits of GABAA receptors have made important advances in the understanding of the action of benzodiazepines, ethanol and neurosteroids. Glycine receptors are composed principally by α1-3 subunits and the auxiliary subunit β determines their synaptic location and their pharmacological response to propofol and ethanol. NMDA receptors appear to be functional as heterotetrameric channels. So far, the existence of NMDA auxiliary subunits is controversial. On the other hand, Kainate receptors are modulated by NETO 1 and 2. AMPA receptors are modulated by TARPs, Shisa 9, CKAMP44, CNIH2-3 auxiliary proteins reported that controls their trafficking, conductance and gating of channels. P2X receptors are able to associate with auxiliary Pannexin-1 protein to modulate P2X7 receptors. Considering the pharmacological relevance of different LGICs auxiliary subunits in the present work we will highlight the therapeutic potential of these modulator proteins.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Galaz
authors.affiliation: Laboratory of Neurochemistry, Medicine School, Faculty of Medical Sciences, University of Santiago of Chile, Chile.
authors.forename: Rafael
authors.initials: R
authors.lastname: Barra
authors.affiliation: Department of Basic and Medical Sciences, Faculty of Health Sciences, University of Talca, Chile.
authors.forename: Hector
authors.initials: H
authors.lastname: Figueroa
authors.affiliation: Center For Medical Research, School of Medicine, University of Talca, Chile. Electronic address: tmariqueo@utalca.ca.
authors.forename: Trinidad
authors.initials: T
authors.lastname: Mariqueo
mesh_terms: D000818:Animals; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D058446:Ligand-Gated Ion Channels / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008958:Models, Molecular; D021122:Protein Subunits; D018091:Receptors, AMPA / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D017470:Receptors, Glutamate / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D018009:Receptors, Glycine / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D058469:Receptors, Purinergic P2X / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism
chemical_list: D058446:Ligand-Gated Ion Channels; D021122:Protein Subunits; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D018009:Receptors, Glycine; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; D058469:Receptors, Purinergic P2X; D044406:Receptors, Serotonin, 5-HT3
keywords: Auxiliary subunits; LGICs; Pharmacological modulation