Interaction between diffusion and Michaelis-Menten uptake of dopamine after iontophoresis in striatum

Biophys J. 1995 May;68(5):1699-715. doi: 10.1016/S0006-3495(95)80348-6.

Abstract

A quantitative description of the behavior of a neurotransmitter in the brain extracellular microenvironment requires an understanding of the relative importance of diffusion versus uptake processes. This paper models the behavior of dopamine released from a small iontophoresis electrode and its voltammetric detection by a carbon fiber sensor 100 microns away as a basis for developing a new paradigm for measuring dopamine kinetics in intact rat neostriatum. The diffusion equation incorporating uptake, characterized by a maximum velocity Vmax and a Michaelis-Menten constant Km, was transformed to an integral equation and solved numerically for the dopamine concentration, C. Analytical solutions were derived for limiting cases of a steady-state free-boundary problem when C >> Km and the linear time-dependent problem when C << Km. These solutions were compared with complete numerical solutions, both for normal uptake (Vmax = 0.2 or 0.8 microM s-1; Km = 0.15 microM), and in the presence of the uptake blocker nomifensine (Km = 6 microM). The results suggest that an experimental strategy for the quantitative analysis of dopamine, and other compounds, in living tissue is to fit a family of concentration versus time curves generated with different iontophoretic current strengths and recorded with a microsensor, to the numerical solution of the diffusion-uptake equation.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Transport
  • Corpus Striatum / metabolism*
  • Diffusion
  • Dopamine / administration & dosage
  • Dopamine / metabolism*
  • Extracellular Space / physiology
  • In Vitro Techniques
  • Iontophoresis
  • Kinetics
  • Mathematics*
  • Mice
  • Models, Biological*
  • Rats
  • Synaptosomes / metabolism*
  • Thermodynamics
  • Time Factors

Substances

  • Dopamine