Neurotransmitter release is a key feature of neurotransmission in central neurons. Although the mechanism of synaptic vesicle release in active zones is not known, it is recognized that calcium channels play an important role in the delivery of the rapid transient calcium signal required for vesicle release. The structural basis for the role of calcium channels in synaptic vesicle release has been recently implicated by data indicating specific protein-protein interactions between both N-type and P/Q-type channels and the synaptic proteins, syntaxin and SNAP-25. A functional role for these interactions has been suggested by experiments in paired superior cervical ganglion cells, in which the introduction of the binding region of the N-type calcium to the synaptic proteins into the pre-synaptic cell resulted in modulation of synaptic transmission. This present project involve further delineation of the binding region of calcium channels to the synaptic proteins. One of the goals is the discovery of the minimal DNA and protein sequences necessary for the specific interaction between the calcium channels and synaptic proteins. Another goal is the further exploration of the previously demonstrated calcium dependence of the interaction between the N-type calcium channel and the synaptic proteins. Another goal is the further exploration of the previously demonstrated calcium dependence of the interaction between the N-type calcium channel and the synaptic proteins. Minimal sequences required for the calcium dependent interaction will also be investigated. A further goal of this project is to examine the function role of the protein-protein interactions between the calcium channels and synaptic proteins in central synaptic transmission. Hippocampal primary cultures will be established that will allow investigation of the effect of N-type and P/Q type peptides in neural transmission. The successful resolution of some of these goals will have important implications not only in the important study of the mechanisms of synaptic transmission, which are crucial for cognitive processes and memory formation; but in a broad range of clinically relevant issues such as regeneration in chronic degenerative diseases to limiting damage from trauma or ischemia.
