A high affinity choline transport system has been characterized as an essential element in supporting of cholinergic transmission. This transporter has a obligatory requirement for, and co-transports sodium (ChCoT). An important feature of this co-transporter is that the transport activity appears to adjust neuronal activity. The adjustment of ACh to be met and thus is physiologically highly significant. The precise molecular mechanisms responsible for this physiological regulation of the ChCoT are not well understood. We propose a three part hypothesis to explain this physiological regulation of the ChCoT. The first part of our proposed hypothesis is that the changes in the transport rates of choline at the cholinergic synapse reflect parallel changes in the number of active ChCoTs in the plasma membrane. The second part of the hypothesis is that the number of ChCoTs is the terminal (plasma) membrane in determined by the regulated and constitutive cycling of carrier vesicles containing ChCoTs is the terminal (plasma) membrane in determined by the regulated and constitutive cycling of carrier vesicles containing ChCoTs between a cytosolic compartment between the cytosol and the plasma membrane is under the influence of intracellular messengers. To test this three part hypothesis we will accomplish the following set of Specific Aims. 1. Establish the vesicular nature of the cycling ChCoT and characterize the molecular mechanisms involved in this cycling. 2. Determine the molecular mechanism of protein kinase C (PKC) involvement in the cycling of ChCoT vesicles. 3. Isolate,, purify and initiate the characterization of the carrier vesicle that serves as the cytoplasmic source of the recruitable pool of ChCoTs.
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