Detection and imaging of zinc secretion from pancreatic beta-cells using a new fluorescent zinc indicator

J Am Chem Soc. 2002 Feb 6;124(5):776-8. doi: 10.1021/ja011774y.

Abstract

A novel Zn2+-selective visible wavelength fluoroionophore (FluoZin-3, 9) was synthesized. The chelating portion of the molecule resembles known EGTA-based Ca2+-selective fluoroionophores, except that one of the N-acetic acid moieties has been deleted in 9. FluoZin-3 is virtually non-fluorescent in the absence of Zn2+, and exhibits a several hundred-fold fluorescence increase upon saturation with Zn2+( approximately 100 nM), with a Kd = 15 +/- 2 nM. A 1:1 binding stoichiometry of 9:Zn2+ was determined, and the fluorescence of the complex is pH-independent at pH > 6. FluoZin-3 was used to monitor Zn2+ that was co-secreted with insulin from pancreatic beta-cells by exocytosis following stimulation with glucose. The total Zn2+ concentration near the cells reached 600 nM, and Zn2+ was detectable at least 15 mum away from secreting cells. Heterogeneity in secretion among cells was indicated in that some cells in a cluster did not release Zn2+. Also, within secreting cells some regions of the cell membrane gave rise to secretion while others did not, suggesting active zones of secretion on the cell surface.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cations, Divalent
  • Fluorescent Dyes / chemistry*
  • Humans
  • Islets of Langerhans / chemistry
  • Islets of Langerhans / metabolism*
  • Kinetics
  • Microscopy, Confocal
  • Polycyclic Compounds / chemistry
  • Spectrometry, Fluorescence
  • Zinc / analysis
  • Zinc / chemistry
  • Zinc / physiology*

Substances

  • Cations, Divalent
  • FluoZin-3
  • Fluorescent Dyes
  • Polycyclic Compounds
  • Zinc