Ion Channel-Coupled Receptors

Abstract

Conduction of nerve impulse is a major signalling pathway in multicellular organisms and requires ion channels situated at the level of plasma membranes of excitable cells. Opening and closing of these channels are controlled by the level of membrane polarisation, and this explains their generic name of voltage-operated channels (VOC). At the level of synapses, nerve impulse transduction from a neuron to another one or to a muscle cell is operated through the release, in the synaptic cleft, of signals that activate the opening of other ion channels. These are called receptor-operated channels (ROC), ionotropic receptors or ligand-gated ion channels (LGIC). Their ligands are neurotransmitters: acetylcholine, serotonin, amino acids and purine nucleotides (ATP). They can in addition react with intracellular proteins (small G-proteins, cytoplasmic tyrosine kinases) and with cytoskeletal proteins. Outside the nervous tissues, they can behave as signalling molecules in many cell types.

Receptor-activated ion channels are also present within the cells and enable especially the transfer of Ca²⁺ ions from one compartment to another one. Calcium signalling has been mentioned in Chap. 6: the second messenger resulting from GPCR (G-protein-coupled receptors) activation leads to Ca²⁺ release in the cytosol, which enables this ‘third messenger’ to activate numerous effectors, which play a major role in muscle contraction and secretion processes.

We will not detail here all the aspects of the signalling operated by ionic fluxes, which pertain to neurosciences rather than to oncology; after a simplified presentation of LGIC in excitable cells, we will focus on two special types of channel receptors: purinergic receptors and receptors enabling intracellular Ca²⁺ mobilisation.