DAncing past the DAT at a DA synapse

Abstract

Spillover of dopamine (DA) from a release site into the extrasynaptic space is widely acknowledged. Indeed, spillover is necessary for signalling by DA because its receptors are predominantly extrasynaptic. Dopamine transporters (DATs) are often considered to participate in this process by 'gating' spillover. This article reviews the competition between DATs and diffusion in sculpting extracellular DA transients after quantal release, using a model based on data from the literature. Its conclusions challenge the view that DATs limit synaptic DA concentration and gate initial spillover from a release site; this is the work of diffusion. Rather, the greatest influence of DATs, or of their inhibition, is on the sphere of influence and lifetime of DA beyond a release site and, thus, on net extracellular concentration.