Neurosecretory Granular Ca2+ Release Affects Exocytosis

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DESCRIPTION (provided by applicant): Recent work has shown that highly localized Ca2+ release events, like Ca2+ sparks of the muscle, can be seen in neuronal preparations. In neurohypophysial terminals, these Ca2+ release events appear to emanate from a ryanodine sensitive intracellular Ca2+ pool, and depolarizing stimuli induces an increase in their frequency. In spite of all this information, the source of the released Ca2+, and a physiological role of this phenomenon is unknown. Preliminary evidence suggests that these Ca2+ release events could represent mobilization of Ca2+ from vesicular stores. If so, localized Ca2+ release in the precise location of exocytosis must modulate release. It is my goal to determine the source of these ryanodine sensitive Ca2+ release events in neurohypophysial terminals, and to show that this mobilization of Ca2+ modulates neuropeptide secretion. This project aims to add to the current body of knowledge of the physiology of the neurohypophysial terminals, and also to provide a more complete understanding of the mechanism by which granular fusion occurs in the CMS. This knowledge could prove to be important for the understanding and treatment of synaptic pathologies such as Eaton-Lambert syndrome, and Amyotrophic lateral sclerosis.