Role of P2X and P2Y ATP Receptors in Neuromuscular Development

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

0077634 Hume Nerve cells communicate information to each other at narrow zones of contact referred to as synapses. The incoming presynaptic cell releases a chemical signal (the neurotransmitter), which binds to receptors on the target cell, eliciting electrical excitation or inhibition. The general goal of these experiments is to understand the mechanisms that allow developing synapses to reach their stable, mature state. The principal hypothesis to be explored is that in addition to the two signals known to pass between nerve and muscle to promote synapse maturation (agrin and ARIA), an additional signaling system also transmits key information. This proposed signaling system consists of ATP (adenosine 5' triphosphate) released from presynaptic terminals interacting with two different types of ATP receptors on the muscle cell surface. The hypothesis will be tested by using molecular biological and pharmacological tools to alter the function of the ATP receptors on the surface of chick muscle cells developing within the egg, and in cell culture. It is important that mature neuromuscular synapses be stable, so that they can reliably control of the routine actions of the nervous system such as commanding muscles to move in the pattern that allows us to breathe. However, understanding the mechanisms that promote synaptic growth and maturation are likely to also provide us with insight into the mechanisms that bring about changes in synaptic function in other regions of the mature nervous system where synapses are not always stable. Changes in the amplitude of synaptic responses are thought to be the cellular basis by which learning and forgetting occur.