We propose to investigate two aspects of neuromuscular physiology in frogs and in mice. 1). Plasticity of quantal size. Quantal size can be increased by hormones or by nerve stimulation, and it seems likely that such changes play a role in the operation of the nervous system. Size is increased by the release of more acetylcholine (ACh)/quantum. We will investigate the mechanism for the size increases and the mechanism by which the additional ACh is released. In some circumstances some of the ACh may be released by a mechanism other than exocytosis. The mechanism for this additional release will be compared to that for the nonquantal leak of ACh at the mouse neuromuscular junction. We will also use """"""""false transmitters"""""""" to follow changes in ACh metabolism as quantal size is changed. Certain anions, like gluconate, potentiate the increase in quantal size. Other anions, like propionate, depress the increase in quantal size. The mechanism(s) for the action of these anions will be investigated. Once increased, quantal size can be down regulated to normal by treatments that produce a sustained elevation in [Ca2+] in the nerve terminals. Preliminary results suggest that down regulation follows activation of protein kinase C. The second messengers involved in both the increase and decrease in quantal size will be studied. 2). Mechanism of facilitation. We have found that facilitation is markedly enhanced at 0 degrees Centigrade. Facilitation is believed to be due to residual Ca2+ in the nerve terminals. Following an end-plate potential, there is a transitory increase in the rate of spontaneous quantal release-- delayed release, which is also thought due to residual Ca2+. By measuring facilitation and delayed release at different temperatures we propose to test the residual Ca2+ hypothesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS010320-18A1
Application #
3394212
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1976-09-01
Project End
1995-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
18
Fiscal Year
1990
Total Cost
Indirect Cost
Name
State University New York Stony Brook
Department
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794