Improved Calibration of Voltammetric Sensors for Studying Pharmacological Effects on Dopamine Transporter Kinetics in Vivo

Christopher W. Atcherley, Nicholas D. Laude, Eric B. Monroe, Kevin M. Wood, Parastoo Hashemi, Michael L Heien

Research output: Contribution to journalArticle

16 Scopus citations

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 K<inf>M</inf> for the murine dopamine transporter. The K<inf>M</inf> 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.

Original languageEnglish (US)
Pages (from-to)1509-1516
Number of pages8
JournalACS Chemical Neuroscience
Volume6
Issue number9
DOIs
StatePublished - Jul 25 2014

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Keywords

  • calibration
  • Dopamine
  • electrochemistry
  • hindered diffusion
  • in vivo
  • kinetics

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Physiology
  • Cognitive Neuroscience

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