The goal of the proposed research is to understand some of the fundamental properties of mammalian presynaptic nerve terminals. Pinched-off nerve endings (synaptosomes) isolated from rat brain will be used, because they retain many functional, metabolic, and morphological properties of intact neuronal tissue, and are well-suited for studies that involve radiotracer-flux, optical, and biochemical techniques. The Investigator will: 1) examine the characteristics of the presynaptic Ca channels involved in neurosecretion - permeability and selectivity, and mechanism of inactivation; 2) determine how cations that permeate, and selectively block, Ca channels influence Ca sequestration and extrusion and transmitter release; 3) measure intracellular pH in the nerve terminals, study how it is regulated, and how it is related to Ca channel activity and neurosecretion; 4) develop and utilize methods for loading Ca-indicators into nerve terminals, so that Ca metabolism and its relation to the activity of nerve terminals can be investigated. This project will provide a better understanding of the basic cellular mechanisms that control intracellular Ca and pH in brain nerve endings, and of how this regulation affects the relase of brain neurotransmitters.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020464-03
Application #
3400798
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1983-12-01
Project End
1987-12-31
Budget Start
1985-12-01
Budget End
1987-12-31
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Type
Schools of Medicine
DUNS #
201373169
City
New York
State
NY
Country
United States
Zip Code
10065
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