Control of neuronal excitability by Group I metabotropic glutamate receptors

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 Gα_q, 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.

Keywords: Action potential; HCN channels; KIR channels; Na+/Ca2+ exchanger; Neuron; SK channels; TRPC channels; mGlu receptor.