dizocilpine-maleate and sulforhodamine-101

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.

Topics: Animals; Biophysics; Chelating Agents; Dizocilpine Maleate; Dopamine; Dopamine Agonists; Egtazic Acid; Electric Stimulation; Electrochemistry; Excitatory Amino Acid Antagonists; Female; G Protein-Coupled Inwardly-Rectifying Potassium Channels; GABA Antagonists; In Vitro Techniques; Inhibitory Postsynaptic Potentials; Male; Mice; Mice, Inbred DBA; Neurons; Patch-Clamp Techniques; Phosphinic Acids; Picrotoxin; Propanolamines; Quinoxalines; Quinpirole; Rhodamines; Signal Transduction; Statistics, Nonparametric; Temperature; Time Factors; Ventral Tegmental Area