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

The possible voltage-dependence of the dopamine transporter (DAT) was inves tigated using electrophysiological and electrochemical recordings in rat br ain slices containing the substantia nigra (SN). Whole-cell patch clamp rec ordings of DA neurons, revealed that addition of 15 mM KCl rapidly depolari zed the membrane potential by similar to 20 mV, whereas these cells were hy perpolarized similar to 10 mV by DA (10 mu M) and similar to 14 mV by the G ABA(B)-receptor agonist baclofen (30 mu M). High-speed chronoamperometric r ecordings were used to monitor clearance properties of exogenously applied DA signals during similar manipulations. Superfusion of slices with 15 mM K CI significantly increased the time course of the DA signal, consistent wit h inhibition of DAT activity. Application of the D-2 DA-receptor antagonist sulpiride (50 mu M) also significantly increased the time course, suggesti ng that DA-induced hyperpolarization enhances DAT activity. Baclofen revers ed the effects of sulpiride on DA clearance. These results demonstrate that changes in DA cell membrane potential can modulate DAT activity. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.