Distinct labelling of fusion events in rat lactotrophs by FM 1-43 and FM 4-64 is associated with conformational differences

Acta Physiol (Oxf). 2007 Sep;191(1):35-42. doi: 10.1111/j.1748-1716.2007.01716.x. Epub 2007 Jun 5.

Abstract

Aim: Conformational analysis of fluorescent styryl dyes FM 1-43 and FM 4-64 was undertaken to clarify if distinct activity-dependent labelling of single lactotrophs vesicles and plasma membrane by two dyes is associated with their structural differences.

Methods: The activity-dependent labelling of single vesicles and plasma membrane by FM 1-43 and FM 4-64 was studied using confocal microscopy. The fluorescence intensity of vesicles fused with the plasma membrane, and the plasma membrane alone was measured; the ratio of their respective peak amplitudes was calculated. The conformational analysis of FM 1-43 and FM 4-64 was further undertaken by employing the Monte Carlo approach to search the conformational space of these molecules.

Results: In FM 1-43 staining of vesicles and plasma membrane, the ratio of the fluorescence peak amplitudes (vesicle vs. plasma membrane) was 2.6 times higher in comparison with FM 4-64 staining. In FM 4-64 molecule the low-energy conformations are distributed in three conformational states (consisting of 3, 4 and 2 conformers respectively) in which the proportion of the molecules residing in a given state is 62%, 28% and 9% respectively. In FM 1-43 the conformation distribution is limited to just one conformational state with three approximately equally populated conformers what can be explained by greater intrinsic rigidity of the molecule.

Conclusions: The observed structural characteristics of FM 1-43 molecules may account for a higher increase in quantum yield and/or binding affinity upon incorporation of the dye into the vesicle matrix and therefore stronger fluorescence emission in comparison with FM 4-64.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Membrane / ultrastructure
  • Cells, Cultured
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / pharmacology*
  • Lactotrophs / drug effects
  • Lactotrophs / metabolism
  • Lactotrophs / ultrastructure*
  • Male
  • Membrane Fusion
  • Microscopy, Confocal
  • Molecular Conformation
  • Potassium / pharmacology
  • Protein Binding
  • Pyridinium Compounds / chemistry
  • Pyridinium Compounds / pharmacology*
  • Quaternary Ammonium Compounds / chemistry
  • Quaternary Ammonium Compounds / pharmacology*
  • Rats
  • Rats, Wistar
  • Secretory Vesicles / ultrastructure
  • Staining and Labeling

Substances

  • FM 4-64
  • FM1 43
  • Fluorescent Dyes
  • Pyridinium Compounds
  • Quaternary Ammonium Compounds
  • Potassium