Coexistence and function of different neurotransmitter transporters in the plasma membrane of CNS neurons

Transporters able to recapture released neurotransmitters into neurons can no longer be considered as cell-specific neuronal markers. In fact, colocalization on one nerve terminal of transporters able to selectively recapture the released endogenously synthesized transmitter (homotransporters) and of transporters that can selectively take up transmitters/modulators originating from neighboring structures (heterotransporters) has been demonstrated to occur on several families of nerve terminals. Activation of heterotransporters often increases the release of the transmitter stored in the terminals on which the heterotransporters are localized. The release caused by heterotransporter activation takes place through multiple mechanisms including exocytosis, either dependent on external Ca(2+) or on Ca(2+) mobilized from intraterminal stores, and homotransporter reversal. Homocarrier-mediated release elicited by heterocarrier activation represents a clear case of transporter-transporter interaction. Although the functional significance of transporter coexpression on one nerve terminal remains to be established, it may in some instances reflect cotransmission. In other cases, heterotransporters may mediate modulation of basal transmitter release in addition to the modulation of the evoked release brought about by presynaptic heteroreceptors. Heterotransporters are also increasingly reported to exist on neuronal soma/dendrites. With the exception of EAAT4, the glutamate transporter/chloride channel situated on GABAergic Purkinje cells in the cerebellum, the functions of somatodendritic heterocarriers is not understood.