Control of neuronal excitability by Group I metabotropic glutamate receptors
- PDF / 621,330 Bytes
- 11 Pages / 595.276 x 790.866 pts Page_size
- 86 Downloads / 174 Views
REVIEW
Control of neuronal excitability by Group I metabotropic glutamate receptors Ana Maria Bernal Correa 1 & Jennifer Diniz Soares Guimarães 1 & Everton dos Santos e Alhadas 1 & Christopher Kushmerick 1,2
Received: 1 June 2017 / Accepted: 27 July 2017 # International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany 2017
Abstract Metabotropic glutamate (mGlu) receptors couple through G proteins to regulate a large number of cell functions. Eight mGlu receptor isoforms have been cloned and classified into three Groups based on sequence, signal transduction mechanisms and pharmacology. This review will focus on Group I mGlu receptors, comprising the isoforms mGlu1 and mGlu5. Activation of these receptors initiates both G protein-dependent and -independent signal transduction pathways. The G-protein-dependent pathway involves mainly Gαq, which can activate PLCβ, leading initially to the formation of IP3 and diacylglycerol. IP3 can release Ca2+ from cellular stores resulting in activation of Ca2+-dependent ion channels. Intracellular Ca2+, together with diacylglycerol, activates PKC, which has many protein targets, including ion channels. Thus, activation of the G-protein-dependent pathway affects cellular excitability though several different effectors. In parallel, G protein-independent pathways lead to activation of non-selective cationic currents and metabotropic synaptic currents and potentials. Here, we provide a survey of the membrane transport proteins responsible for these electrical effects of Group I metabotropic glutamate receptors.
This article is part of a Special Issue on ‘Latin America’ edited by Pietro Ciancaglini and Rosangela Itri. * Christopher Kushmerick [email protected] 1
Graduate Program in Physiology and Pharmacology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
2
Departamento de Fisiologia e Biofísica – ICB, UFMG, Av. Pres. Antônio Carlos, 6627 – Pampulha, Belo Horizonte, MG 31270-901, Brazil
Keywords Neuron . mGlu receptor . Action potential . HCN channels . KIR channels . TRPC channels . Na+/Ca2+ exchanger . SK channels
Introduction This article reviews actions of Group I metabotropic glutamate receptors (mGlu) on neuronal excitability. This group of receptors, comprising mGlu1 and mGlu5, share sequence homology, coupling through protein Gαq/11, pharmacology, and post-synaptic localization that distinguish them from the other six mGlu isoforms found in the mammalian genome (Cartmell and Schoepp 2000; Foord et al. 2005; Nakanishi 1992). Our focus is on short-term changes in membrane current that directly result from Group I mGlu receptor activation and the subsequent mobilization of second messenger systems. The goal is an understanding of how these currents affect neuronal excitability and of their physiological roles. In addition to direct modulation of post-synaptic membrane currents and excitability described here, Group I mGlu receptors have many other important roles in the nervous system. Their activation can trigger release
Data Loading...
