DEVELOPMENTAL REGULATION OF MULTIPLE NICOTINIC ACHR CHANNEL SUBTYPES IN EMBRYONIC CHICK HABENULA NEURONS - CONTRIBUTIONS OF BOTH THE ALPHA-2 AND ALPHA-4 SUBUNIT GENES

Habenula neurons from both early and late stage embryonic chickens express multiple subtypes of nicotinic acetylcholine receptor channels (nAChRs). The channel subtypes expressed by habenula neurons are similar in functional properties, but apparently distinct in subunit composition, from their peripheral counterparts in autonomic ganglia. Early in development, nicotine activates four classes of neuronal bungarotoxin (nBGT)-sensitive channels (approx. conductance=15, 30, 50, 60pS) that are intermingled on the surface of habenula neuronal somata. In neurons removed from older animals, nAChR channel activity has increased 4- to 40-fold and channel subtypes have become spatially segregated from one another. Analysis of the profile of nAChR subunit gene expression by polymerase chain reaction indicates that several of the alpha-type subunit genes, including alpha 2,3,4,5,7, and alpha 8, as well as both beta 2 and beta 4, are expressed. Treatment of the neurons with subunit specific antisense oligonucleotides reveals that the alpha 2 and alpha 4 (but not alpha 3) subunits contribute to the functional profile of native nAChRs expressed by habenula neurons. Consideration of the functional properties and apparent subunit composition of autonomic ganglion nAChRs in the chick suggests that habenula neurons may utilize a very distinct set of subunit combinations to produce an array of nAChR channel subtypes similar in both conductance and pharmacological profile to those expressed by sympathetic neurons.