Microscopic kinetics and structure-function analysis in the vesicular acetylcholine transporter.
The vesicular acetylcholine transporter (VAChT) resides in synaptic vesicles of cholinergic nerve terminals. It carries out vesicular storage of ACh. The amount of ACh stored determines, along with other factors, the amount of ACh released. Knowledge of the structure-function relationship in VAChT might enable pharmacological regulation of ACh storage and release at the level of VAChT. To this end, a quantitative model for the individual steps in the overall transport cycle of VAChT has been developed. Because of the particular values of the microscopic rate constants in the model, structure-function analysis of VAChT can be misleading. Attempts to devise a pro-storage strategy to increase ACh release from cholinergic nerve terminals should take into account the microscopic kinetics of this transporter.
Bravo
Dawn
D
Department of Chemistry and Biochemistry, The Neuroscience Research Institute, University of California, 93106-9510, Santa Barbara, CA, USA
Parsons
Stanley M
SM
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D026901:Membrane Transport Proteins; D008954:Models, Biological; D009154:Mutation / Q000502:physiology; D013329:Structure-Activity Relationship; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D026901:Membrane Transport Proteins; C493459:SLC18A3 protein, human; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins