A fundamental problem in the neurosciences is the characterization of the mechanism(s) controlling the release of neurotransmitters and neurohormones at nerve endings. These mechanisms are crucial to nerve cell communication and to a healthy, functioning nervous system. Although the importance of calcium's role in release has been well established, details in its action are poorly understood. This research project is designed to examine, quantitatively, the relationship between calcium currents and intracellular calcium concentrations. Moreover, receptor mediated regulation of the calcium current and its effect on intracellular calcium levels will be directly evaluated. Electrophysiological techniques combined with microspectrofluorometry of calcium sensitive, fluorescent indicators will be used to monitor intracellular calcium levels. Techniques will be developed to allow simultaneous monitoring of neurohormone release from single endings. This research will lead to a better understanding of the properties and actions of molecular components regulating neurohormone release from vertebrate nerve endings.