9514421 Thompson Understanding the functioning of messenger molecules inside cells is critical for a complete explanation of how nerve cells communicate. Activation of molecular receptors on the surface of nerve cells by neurotransmitter molecules unleashes a cascade of events, which is orchestrated by the intracellular messengers. The key messenger is the concentration of calcium ions, which controls the production of the gaseous neurotransmitter, nitric oxide (NO). Nitric oxide, in turn, stimulates the production of the cyclic nucleotide messenger, cGMP. Calcium ions, NO, and cGMP together regulate numerous physiological events, including synaptic transmission and the opening of membrane ion channels. The focus of this research project is on the dynamics of calcium ion concentrations, which are affected by calcium release from intracellular storage compartments and by calcium ion inflow through the cell membrane. More specifically, the experiments are concerned with the internal signaling pathway that is activated by muscarinic cholinergic receptors in cultured cells. Techniques employed include the voltage clamp and calcium imaging; these are combined with modern molecular techniques to examine in detail rate-limiting steps in the activation of calcium release, for calcium influx, and in the production of cGMP. It is expected that these experiments will greatly advance our understanding of fundamental cellular mechanisms that regulate signaling within nerve cells.
