MOLECULAR CHARACTERIZATION AND FUNCTIONAL EXPRESSION OF MOLLUSCAN ION-CHANNEL RECEPTORS THAT CAN BE ACTIVATED BY EITHER GAMMA-AMINOBUTYRIC-ACID OR L-GLUTAMATE

Ligand-gated ion channels (also called ionotropic receptors) are a cla ss of receptors which possess an intrinsic ion pore, selective for eit her cations or anions, that can be opened by the binding of an appropr iate neurotransmitter. Ionotropic receptors for gamma-aminobutyric aci d (GABA) and L-glutamate have been extensively characterised in the ve rtebrate nervous system, at the molecular level, through the applicati on of recombinant DNA techniques. These studies have shown that subtyp es of GABA receptors (which are inhibitory) and glutamate receptors (w hich are excitatory) occur, and that these probably all exist in vivo as hetero-oligomers. Although there is ample evidence for the existenc e of ligand-gated ion channels in invertebrate nervous tissue and musc les, progress in their molecular definition has been comparatively slo w. In an effort to determine the nature and specific biological functi ons of glutamate and GABA receptors in molluscs, we have isolated comp lementary DNAs (cDNAs), from Lymnaea stagnalis, that encode components of these ion channels. To date, we have obtained full-length cDNAs fo r three different polypeptides that are similar in sequence to vertebr ate GABA type A (GABA(A)) receptor subunits, and three different polyp eptides that resemble vertebrate glutamate-gated ion-channel subunits. In addition, we have isolated partial clones for five other GABA(A) r eceptor-like polypeptides and two further glutamate receptor-like poly peptides. Here we describe the isolation of these clones, and the elec trophysiological and pharmacological properties of channels that are f ormed upon the expression of some of these cDNAs in Xenopus laevis ooc ytes.