MULTIPLE ACTIVITY PATTERNS OF ACETYLCHOLINE RECEPTORS

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The central observation upon which this proposal is based is that in embryonic amphibian muscle cells, acetylcholine receptor channels of similar conductance have multiple kinetic forms. The specific aims are: 1) to quantify the molecular rate constants which govern transmitter binding and channel gating in different kinetic forms of channel, 2) to determine if channels can change kinetic mode, either as individuals or as a population, and 3) to ascertain if and how kinetic hererogeneity in cholinergic channels relates to myocyte development and the assembly of the neuromuscular synapse. The major experimental method will be patch clamp electrophysiology and single-channel data analysis. The research is significant because it will compliment studies of structure-function relationships in cholinergic channels, it will give insight into the molecular and cellular mechanisms by which an ion channel's kinetic properties are modulated, and it will provide a high resolution view of changes in the properties of a transmitter-gated ion channel during muscle and synapse development.