title: Improved Calibration of Voltammetric Sensors for Studying Pharmacological Effects on Dopamine Transporter Kinetics in Vivo.
abstract: The distribution and density of neurons within the brain poses many challenges when making quantitative measurements of neurotransmission in the extracellular space. A volume neurotransmitter is released into the synapse during chemical communication and must diffuse through the extracellular space to an implanted sensor for real-time in situ detection. Fast-scan cyclic voltammetry is an excellent technique for measuring biologically relevant concentration changes in vivo; however, the sensitivity is limited by mass-transport-limited adsorption. Due to the resistance to mass transfer in the brain, the response time of voltammetric sensors is increased, which decreases the sensitivity and the temporal fidelity of the measurement. Here, experimental results reveal how the tortuosity of the extracellular space affects the response of the electrode. Additionally, a model of mass-transport-limited adsorption is utilized to account for both the strength of adsorption and the magnitude of the diffusion coefficient to calculate the response time of the electrode. The response time is then used to determine the concentration of dopamine released in response to salient stimuli. We present the method of kinetic calibration of in vivo voltammetric data and apply the method to discern changes in the KM for the murine dopamine transporter. The KM increased from 0.32 ± 0.08 μM (n = 3 animals) prior to drug administration to 2.72 ± 0.37 μM (n = 3 animals) after treatment with GBR-12909.
authors: Department of Chemistry and Biochemistry, University of Arizona , 1306 East University Boulevard, Tucson, Arizona 85721, United States.
authors: Christopher W
authors: CW
authors: Atcherley
authors: Department of Chemistry and Biochemistry, University of Arizona , 1306 East University Boulevard, Tucson, Arizona 85721, United States.
authors: Nicholas D
authors: ND
authors: Laude
authors: Department of Chemistry and Biochemistry, University of Arizona , 1306 East University Boulevard, Tucson, Arizona 85721, United States.
authors: Eric B
authors: EB
authors: Monroe
authors: Department of Chemistry, Wayne State University , 5101 Cass Avenue, Detroit, Michigan 48202, United States.
authors: Kevin M
authors: KM
authors: Wood
authors: Department of Chemistry, Wayne State University , 5101 Cass Avenue, Detroit, Michigan 48202, United States.
authors: Parastoo
authors: P
authors: Hashemi
authors: Department of Chemistry and Biochemistry, University of Arizona , 1306 East University Boulevard, Tucson, Arizona 85721, United States.
authors: Michael L
authors: ML
authors: Heien
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002138:Calibration; D003198:Computer Simulation; D004058:Diffusion; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D004563:Electrochemistry / Q000295:instrumentation / Q000379:methods*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D058542:Implantable Neurostimulators; D007700:Kinetics; D008297:Male; D008810:Mice, Inbred C57BL; D008839:Microelectrodes; D008959:Models, Neurological; D010879:Piperazines / Q000494:pharmacology
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; C043425:vanoxerine; D004298:Dopamine
keywords: Dopamine; calibration; electrochemistry; hindered diffusion; in vivo; kinetics