Diverse voltage-sensitive dyes modulate GABAA receptor function

J Neurosci. 2010 Feb 24;30(8):2871-9. doi: 10.1523/JNEUROSCI.5607-09.2010.

Abstract

Voltage-sensitive dyes are important tools for assessing network and single-cell excitability, but an untested premise in most cases is that the dyes do not interfere with the parameters (membrane potential, excitability) that they are designed to measure. We found that popular members of several different families of voltage-sensitive dyes modulate GABA(A) receptor with maximum efficacy and potency similar to clinically used GABA(A) receptor modulators. Di-4-ANEPPS and DiBAC4(3) potentiated GABA function with micromolar and high nanomolar potency, respectively, and yielded strong maximum effects similar to barbiturates and neurosteroids. Newer blue oxonols had biphasic effects on GABA(A) receptor function at nanomolar and micromolar concentrations, with maximum potentiation comparable to that of saturating benzodiazepine effects. ANNINE-6 and ANNINE-6plus had no detectable effect on GABA(A) receptor function. Even dyes with no activity on GABA(A) receptors at baseline induced photodynamic enhancement of GABA(A) receptors. The basal effects of dyes were sufficient to prolong IPSCs and to dampen network activity in multielectrode array recordings. Therefore, the dual effects of voltage-sensitive dyes on GABAergic inhibition require caution in dye use for studies of excitability and network activity.

Publication types

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

MeSH terms

  • Animals
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Female
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / pharmacology*
  • GABA Agents / chemistry
  • GABA Agents / pharmacology*
  • GABA Agonists / pharmacology
  • GABA Antagonists / pharmacology
  • Hippocampus / cytology
  • Hippocampus / metabolism*
  • Inhibitory Postsynaptic Potentials / drug effects
  • Inhibitory Postsynaptic Potentials / physiology
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neurons / drug effects
  • Neurons / metabolism
  • Oocytes
  • Patch-Clamp Techniques
  • Rats
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / metabolism*
  • Staining and Labeling / methods*
  • Synapses / drug effects
  • Synapses / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Voltage-Sensitive Dye Imaging / methods*
  • Xenopus laevis

Substances

  • Fluorescent Dyes
  • GABA Agents
  • GABA Agonists
  • GABA Antagonists
  • Receptors, GABA-A