Abstract
Synaptic transmission mediated by G-protein coupled receptors (GPCR) is not generally thought to be point-to-point. To determine the extent over which dopamine signals in the midbrain, the present study examined the concentration and time course of dopamine that underlies a D(2)-receptor IPSC (D(2)-IPSC) in the ventral tegmental area. Extracellular dopamine was measured electrochemically while simultaneously recording D(2)-IPSCs. The presence of dopamine was brief relative to the IPSC, suggesting that G-protein dependent potassium channel activation determined the IPSC time course. The activation kinetics of D(2) receptor-dependent potassium current was studied using outside-out patch recordings with rapid application of dopamine. Dopamine applied at a minimum concentration of 10 mum for a maximum of 100 ms mimicked the IPSC. Higher concentrations applied for as little as 5 ms did not change the kinetics of the current. The results indicate that both the intrinsic kinetics of G-protein coupled receptor signaling and a rapidly rising high concentration of dopamine determine the time course of the IPSC. Thus, dopamine transmission in the midbrain is more localized then previously proposed.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biophysics
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Chelating Agents / pharmacology
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Dizocilpine Maleate / pharmacology
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Dopamine / metabolism*
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Dopamine / pharmacology
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Dopamine Agonists / pharmacology
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Egtazic Acid / analogs & derivatives
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Egtazic Acid / pharmacology
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Electric Stimulation / methods
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Electrochemistry / methods
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Excitatory Amino Acid Antagonists / pharmacology
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Female
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G Protein-Coupled Inwardly-Rectifying Potassium Channels / physiology
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GABA Antagonists / pharmacology
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In Vitro Techniques
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Inhibitory Postsynaptic Potentials / drug effects
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Inhibitory Postsynaptic Potentials / physiology*
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Male
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Mice
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Mice, Inbred DBA
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Neurons / drug effects
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Neurons / physiology*
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Patch-Clamp Techniques / methods
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Phosphinic Acids / pharmacology
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Picrotoxin / pharmacology
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Propanolamines / pharmacology
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Quinoxalines / pharmacology
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Quinpirole / pharmacology
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Rhodamines / metabolism
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Statistics, Nonparametric
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Temperature
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Time Factors
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Ventral Tegmental Area / cytology*
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Ventral Tegmental Area / physiology*
Substances
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Chelating Agents
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Dopamine Agonists
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Excitatory Amino Acid Antagonists
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G Protein-Coupled Inwardly-Rectifying Potassium Channels
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GABA Antagonists
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Phosphinic Acids
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Propanolamines
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Quinoxalines
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Rhodamines
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Picrotoxin
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CGP 55845A
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Quinpirole
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Egtazic Acid
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FG 9041
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Dizocilpine Maleate
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sulforhodamine 101
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1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
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Dopamine