Chloride requirement for monoamine transporters

This review focuses on the Cl(-) requirement for dopamine, serotonin, and norepinephrine (DA, 5-HT, and NE) transport and induced current via the transporters for these transmitters, DAT, SERT, and NET. Indirect evidence exists for the passage of Cl(-) ions through monoamine transporters; however, direct evidence is sparse. An unanswered question is why in some preparations, notably native neurons, it appears that Cl(-) ions carry the current through DAT, whereas in heterologous expression systems Na(+) ions carry the current often referred to as the uncoupled current. It is suggested that different functional states in monoamine transporters represent conformational states that carry dominantly Cl(-) or Na(+). Structures of monoamine transporters contribute enormously to structure-function relationships; however, thus far no structural features support the functionally relevant ionic currents that are known to exist in monoamine transporters.