Recent studies indicate that N-type and some isoforms of P/Q-type Ca2+ channels bind to presynaptic membrane proteins syntaxin and SNAP-25 and synaptic vesicle protein synaptotagmin, suggesting that presynaptic Ca2+ channels play some roles in vesicle docking, priming, and exocytosis, in addition to providing Ca2+ influx for Ca2+ dependent transmitter release. In accordance with this idea, introduction of peptides containing the synaptic protein interaction (synprint) site of N-type Ca2+ channels into terminals of cultured superior cervical ganglion neurons inhibits synchronous transmitter release. The broad objective of this proposal is to study the functional roles of Ca2+ channel-synaptic protein interactions in central synapses. Autapses of microcultred hippocampal neurons will be used for the studies. Synprint peptides will be delivered to the terminals by ionophoretic injection through whole-cell recording pipette. The types of Ca2+ channels that mediated the autaptic transmission will be identified pharmacologically. Synprint peptides of different Ca2+ channel types will be delivered to the terminals while only one type of Ca2+ channels is allowed to provide Ca2+ influx. The effects of these peptides on autaptic transmission will be monitored by single pulse, paired-pulse modulation, and post-tetanic potentiation protocols. The effects of different types of synprint peptides of Ca2+-independent transmitter release will be probed by hyperosmotic solution stimulation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS010442-02
Application #
2735524
Study Section
Physiology Study Section (PHY)
Program Officer
Talley, Edmund M
Project Start
1998-07-01
Project End
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Washington
Department
Pharmacology
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195