ANALYSIS OF THE EXCITATORY ACTION OF ATP

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Adenosine Triphosphate (ATP) is present in many types of synaptic vesicles, but at most synapses it has not known function. The recent discovery that chick skeletal muscles fibers are excited by ATP (Kolb and Wakelam, 1983; Hume and Honig, 1986) provides an excellent opportunity for examining the role of ATP at synapses, since the neuromuscular junction is by far the best characterized synapse, both in maturity and during development. Muscle cells characterized synapse, both in maturity and during development. Muscle cells in culture are very accessible for electrophysiological and biochemical studies, so these observations also open the way for detailed studies of the cellular and molecular basis of ATP mediated excitation. The specific aims of this project are: 1. To resolve conflicting results regarding the nature of the single channels that underlie the ATP evoked depolarization. 2. To determine whether a second messenger system is involved in the ATP evoked depolarization. 3. To examine the time course and mechanism of the long term desensitization that this response displays. 4. To test the hypothesis that receptor activation involves an extracellular phosphorylation. 5. To determine any functional role that ATP receptors play in neuromuscular transmission or in muscle development. These experiments are designed to further understanding of the function of a receptor found on muscle precursor cells and young muscle cells. The early appearance of this receptor suggests that it may play a role in the development of muscle cells or in the formation of neuromuscular junctions. Knowledge of the cellular interactions that control normal development would provide a basis for understanding, and perhaps ameliorating, medically relevant deficits in nerve and muscle function.