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Review ARTICLE

Front. Physiol., 04 September 2012 | http://dx.doi.org/10.3389/fphys.2012.00319

Extrasynaptic exocytosis and its mechanisms: a source of molecules mediating volume transmission in the nervous system

  • 1Departamento de Neurofisiología, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, México, D.F., México
  • 2Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, D.F., México

We review the evidence of exocytosis from extrasynaptic sites in the soma, dendrites, and axonal varicosities of central and peripheral neurons of vertebrates and invertebrates, with emphasis on somatic exocytosis, and how it contributes to signaling in the nervous system. The finding of secretory vesicles in extrasynaptic sites of neurons, the presence of signaling molecules (namely transmitters or peptides) in the extracellular space outside synaptic clefts, and the mismatch between exocytosis sites and the location of receptors for these molecules in neurons and glial cells, have long suggested that in addition to synaptic communication, transmitters are released, and act extrasynaptically. The catalog of these molecules includes low molecular weight transmitters such as monoamines, acetylcholine, glutamate, gama-aminobutiric acid (GABA), adenosine-5-triphosphate (ATP), and a list of peptides including substance P, brain-derived neurotrophic factor (BDNF), and oxytocin. By comparing the mechanisms of extrasynaptic exocytosis of different signaling molecules by various neuron types we show that it is a widespread mechanism for communication in the nervous system that uses certain common mechanisms, which are different from those of synaptic exocytosis but similar to those of exocytosis from excitable endocrine cells. Somatic exocytosis has been measured directly in different neuron types. It starts after high-frequency electrical activity or long experimental depolarizations and may continue for several minutes after the end of stimulation. Activation of L-type calcium channels, calcium release from intracellular stores and vesicle transport towards the plasma membrane couple excitation and exocytosis from small clear or large dense core vesicles in release sites lacking postsynaptic counterparts. The presence of synaptic and extrasynaptic exocytosis endows individual neurons with a wide variety of time- and space-dependent communication possibilities. Extrasynaptic exocytosis may be the major source of signaling molecules producing volume transmission and by doing so may be part of a long duration signaling mode in the nervous system.

Keywords: exocytosis, extrasynaptic, serotonin, somatic exocytosis, volume transmission, mechanisms of extrasynaptic exocytosis

Citation: Trueta C and De-Miguel FF (2012) Extrasynaptic exocytosis and its mechanisms: a source of molecules mediating volume transmission in the nervous system. Front. Physio. 3:319. doi:10.3389/fphys.2012.00319

Received: 18 April 2012; Paper pending published: 02 May 2012;
Accepted: 21 July 2012; Published online: 04 September 2012.

Edited by:

Kjell Fuxe, Karolinska Institutet, Sweden

Reviewed by:

Kjell Fuxe, Karolinska Institutet, Sweden
A. Del Arco, Universidad Complutense de Madrid, Spain

Copyright © 2012 Trueta and De-Miguel. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

*Correspondence: Citlali Trueta, Departamento de Neurofisiología, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calzada México-Xochimilco 101, Tlalpan 14370, México, D.F., México. e-mail: ctrueta@imp.edu.mx