[Frontiers in Bioscience 17, 2740-2767, June 1, 2012]
Mechanisms of dopamine quantal size regulation
Daniela B. Pereira1, David Sulzer1,2,3
1Department of Neurology, Columbia University School of Medicine, New York, NY 10032, 2 Departments of Psychiatry and Pharmacology, Columbia University School of Medicine, New York, NY 10032, 3Department of Neuroscience, New York Psychiatric Institute, New York, NY 10032
TABLE OF CONTENTS
The study of dopamine (DA) quantal size, or the amount of transmitter released per vesicle fusion event, has been enabled by subsecond resolution amperometric recordings. These methods, together with other electrophysiology techniques, novel optical approaches and classical molecular biology and biochemistry methodologies, have advanced our understanding of quantal size regulation in dopaminergic and other catecholaminergic systems. The presynaptic mechanisms that determine DA quantal size regulate two features: the amount of transmitter stored in each vesicle and the fraction of vesicular contents that are released per fusion event. The amount of vesicular DA is dependent on DA synthesis, DA vesicular loading and storage and on DA reuptake from the extracellular space upon exocytosis. The mode of vesicle fusion and the related fusion pore dynamics control the fraction of DA released per fusion event. We will summarize current understanding on the regulation of these steps by endogenous and exogenous factors, including drugs of abuse and DA itself.