The time course of dopamine transmission in the ventral tegmental area.
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.
Vollum Institute, Oregon Health & Science University, Portland, Oregon 97239, USA.
Christopher P
CP
Ford
Paul E M
PE
Phillips
John T
JT
Williams
D000818:Animals; D001703:Biophysics; D002614:Chelating Agents / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D004563:Electrochemistry / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010721:Phosphinic Acids / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D012235:Rhodamines / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D018709:Statistics, Nonparametric; D013696:Temperature; D013997:Time Factors; D017557:Ventral Tegmental Area / Q000166:cytology* / Q000502:physiology*
D002614:Chelating Agents; D016291:Dizocilpine Maleate; D004298:Dopamine; D018491:Dopamine Agonists; D004533:Egtazic Acid; D018691:Excitatory Amino Acid Antagonists; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D018756:GABA Antagonists; D010721:Phosphinic Acids; D010852:Picrotoxin; D011412:Propanolamines; D011810:Quinoxalines; D019257:Quinpirole; D012235:Rhodamines; C085075:CGP 55845A; C056723:FG 9041; C050829:sulforhodamine 101; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid