Voltage-dependency of the dopamine transporter in the rat substantia nigra.

The possible voltage-dependence of the dopamine transporter (DAT) was investigated using electrophysiological and electrochemical recordings in rat brain slices containing the substantia nigra (SN). Whole-cell patch clamp recordings of DA neurons, revealed that addition of 15 mM KCl rapidly depolarized the membrane potential by approximately 20 mV, whereas these cells were hyperpolarized approximately 10 mV by DA (10 microM) and approximately 14 mV by the GABAB-receptor agonist baclofen (30 microM). High-speed chronoamperometric recordings were used to monitor clearance properties of exogenously applied DA signals during similar manipulations. Superfusion of slices with 15 mM KCl significantly increased the time course of the DA signal, consistent with inhibition of DAT activity. Application of the D2 DA-receptor antagonist sulpiride (50 microM) also significantly increased the time course, suggesting that DA-induced hyperpolarization enhances DAT activity. Baclofen reversed the effects of sulpiride on DA clearance. These results demonstrate that changes in DA cell membrane potential can modulate DAT activity.