Mechanisms of dopamine quantal size regulation.
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.
Department of Neurology, Columbia University School of Medicine, New York, NY 10032, USA. dp2326@columbia.edu
Daniela B
DB
Pereira
David
D
Sulzer
D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008561:Membrane Fusion / Q000502:physiology; D008959:Models, Neurological; D011499:Protein Processing, Post-Translational; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics / Q000378:metabolism
D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D017448:Receptors, Dopamine D2; D050493:Vesicular Monoamine Transport Proteins; D014446:Tyrosine 3-Monooxygenase; D019204:GTP-Binding Proteins; D004298:Dopamine