Role of Dopamine Transporters in Neuronal Homeostasis
Dopamine (DA) neurotransmission is controlled by several critical processes. A complex homeostatic balance between the amount of DA synthesized, packaged into vesicles, released, reuptaken via plasma membrane transporter and metabolized, determines the overall status of dopaminergic signaling. The plasma membrane dopamine transporter (DAT) provides effective control of both the extracellular and intracellular concentrations of DA by recapturing released neurotransmitters in the presynaptic terminals. The vesicular monoamine transporter 2 (VMAT2) directly controls vesicular storage and release capacity by pumping monoamines from the cytoplasm of neurons into synaptic vesicles. These transporters are primary targets of many psychotropic drugs that potently affect synaptic DA and related physiological processes. This chapter summarizes recent advances in the understanding of the molecular and cellular mechanisms involved in the DAT and VMAT2 functions. It discusses the role of these transporters in the action of psychostimulant drugs and neurotoxins, as revealed in studies using mutant mice.
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