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

Alexander F. Hoffman; Nancy R. Zahniser; Carl R. Lupica; Greg A. Gerhardt

doi:10.1016/S0304-3940(98)00951-3

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

Alexander F. Hoffman, Nancy R. Zahniser, Carl R. Lupica, Greg A. Gerhardt

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

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 ~20 mV, whereas these cells were hyperpolarized ~10 mV by DA (10 μM) and ~14 mV by the GABA(B)-receptor agonist baclofen (30 μM). 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 μM) 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.

Original language	English
Pages (from-to)	105-108
Number of pages	4
Journal	Neuroscience Letters
Volume	260
Issue number	2
DOIs	https://doi.org/10.1016/S0304-3940(98)00951-3
State	Published - Jan 29 1999

Bibliographical note

Funding Information:
Supported by National Institutes of Health grants DA04216 and DA00174 (N.R.Z.), NS09199, AG06434, and MH01245 (G.A.G), and DA07725 (C.R.L.). A.F.H. is the recipient of an Advanced Predoctoral Fellowship from the PhRMA Foundation. The authors wish to thank Scott Robinson for manufacturing the electrochemical sensors used in these studies and Dr. Kurt Svoboda for generous assistance in the whole-cell recordings.

Keywords

Baclofen
Brain slice
Dopamine transporter
In vivo electrochemistry
Substantia nigra
Whole-cell patch clamp

ASJC Scopus subject areas

Neuroscience (all)

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10.1016/S0304-3940(98)00951-3

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title = "Voltage-dependency of the dopamine transporter in the rat substantia nigra",

abstract = "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 ~20 mV, whereas these cells were hyperpolarized ~10 mV by DA (10 μM) and ~14 mV by the GABA(B)-receptor agonist baclofen (30 μM). 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 μM) 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.",

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note = "Funding Information: Supported by National Institutes of Health grants DA04216 and DA00174 (N.R.Z.), NS09199, AG06434, and MH01245 (G.A.G), and DA07725 (C.R.L.). A.F.H. is the recipient of an Advanced Predoctoral Fellowship from the PhRMA Foundation. The authors wish to thank Scott Robinson for manufacturing the electrochemical sensors used in these studies and Dr. Kurt Svoboda for generous assistance in the whole-cell recordings.",

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N2 - 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 ~20 mV, whereas these cells were hyperpolarized ~10 mV by DA (10 μM) and ~14 mV by the GABA(B)-receptor agonist baclofen (30 μM). 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 μM) 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.

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

Abstract

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