PHYSIOLOGICAL-PROPERTIES OF NEURONAL NICOTINIC RECEPTORS RECONSTITUTED FROM THE VERTEBRATE BETA-2 SUBUNIT AND DROSOPHILA ALPHA-SUBUNITS

Three cDNAs (ALS, D alpha 2 and ARD) isolated from the nervous system of Drosophila and encoding putative nicotinic acetylcholine receptor s ubunits were expressed in Xenopus oocytes in order to study their func tional properties. Functional receptors could not be reconstituted fro m any of these subunits taken singly or in twos and threes. In contras t, large evoked currents (in the mu A range) were consistently observe d upon agonist application on oocytes co-injected with ALS or D alpha 2 in combination with the chick beta 2 structural subunit. The ALS/bet a 2 and D alpha 2/beta 2 receptors are highly sensitive to acetylcholi ne and nicotine, and their physiological properties resemble those of native or reconstituted receptors from vertebrates. Although the physi ological properties of ALS/beta 2 and D alpha 2/beta 2 receptors are q uite similar, clear differences appear in their pharmacological profil es. The ALS/beta 2 receptor is highly sensitive to a-bungarotoxin whil e the D alpha 2/beta 2 receptor is totally insensitive to this agent. These results demonstrate that the Drosophila ALS and D alpha 2 cDNAs encode neuronal nicotinic subunits responding to physiological concent rations of the agonists acetylcholine and nicotine.