Synaptosomes: A Model System to Study Release of Multiple Classes of Neurotransmitters

Synaptosomes were first isolated by Whittaker (1 ) in 1958 and identified by electron microscopy as detached synapses 2 yr later (2 ). Synaptosomes are sealed particles that contain small, clear vesicles and sometimes larger densecore vesicles, indicating their presynaptic origin. Occasionally, fractions of electron-dense, postsynaptic membranes remain attached to the synaptosomes, facing the active zone. Evidently, synaptosomes contain all the components necessary to store, release, and retain neurotransmitters, the biochemical messengers that effect synaptic transmission. In addition, synaptosomes contain viable mitochondria, enabling production of ATP and active energy metabolism. Ca²⁺ -buffering capacity is retained, as evidenced by the ability of synaptosome preparations to maintain resting internal Ca²⁺ -concentrations of 100–200 nM in the presence of 2 mM extracellular Ca²⁺ (3 ). In addition, synaptosomes maintain a normal membrane potential (which is regulated by a Na⁺ /K⁺ -ATPase) and express functional uptake carriers and ion-channels in their plasma-membranes. On application of diverse depolarizing stimuli (e.g., potassium, veratridine, and 4-aminopyridine), Ca²⁺ enters synaptosomes via high voltage-sensitive Ca²⁺ channels and triggers exocytosis of docked vesicles. Through this process, multiple neurotransmitters (including amino acids, peptides, and catecholamines) are released into the extracellular medium (4 ).