The excitatory role played by nicotinic acetylcholine (AChRs) in autonomic ganglia has been well established. Ganglionic neurons have been shown to express multiple neuronal AChR subunits, but the precise subunit composition of native neuronal AChRs remains unclear. Complete knowledge of the exact subunit composition of native neuronal AChRs is imperative for our understanding of the physiological role played by neuronal AChRs. This proposal is designed to study the structural and functional contributions of particular neuronal AChR subunits in the formation of native human AChRs in the neuroblastoma cell line IMR-32.
The specific aims will address the following questions: What are the functional and pharmacological properties of AChRs expressed in oocytes and how do these properties compare to those for AChRs expressed in IMR-32 cells?; what AChR transcripts are expressed in these cells and how do their levels correlate with AChR surface expression?; what functional impact do particular subunits have on neuronal AChR function?
