Molecular Characterisation and Functional Expression of Molluscan Ion-Channel Receptors That Can Be Activated By Either ?-Aminobutyric Acid or L-Glutamate

Ligand-gated ion channels (also called ionotropic receptors) are a class of receptors which possess an intrinsic ion pore, selective for either cations or anions, that can be opened by the binding of an appropriate neurotransmitter. Ionotropic receptors for ?-aminobutyric acid (GABA) and L-glutamate have been extensively characterised in the vertebrate nervous system, at the molecular level, through the application of recombinant DNA techniques. These studies have shown that subtypes of GABA receptors (which are inhibitory) and glutamate receptors (which are excitatory) occur, and that these probably all exist in vivo as hetero-oligomers. Although there is ample evidence for the existence of ligand-gated ion channels in invertebrate nervous tissue and muscles, progress in their molecular definition has been comparatively slow. In an effort to determine the nature and specific biological functions of glutamate and GABA receptors in molluscs, we have isolated complementary DNAs (cDNAs), from Lymnaea stagnalis, that encode components of these ion channels. ?o date, we have obtained full-length cDNAs for three different polypeptides that are similar in sequence to vertebrate GABA type A (GABAA) receptor subunits, and three different polypeptides that resemble vertebrate glutamate-gated ion-channel subunits. In addition, we have isolated partial clones for five other GABAA receptor-like polypeptides and two further glutamate receptor-like polypeptides. Here we describe the isolation of these clones, and the electrophysiological and pharmacological properties of channels that are formed upon the expression of some of these cDNAs in Xenopus laevis oocytes