Diverse voltage-sensitive dyes modulate GABAA receptor function.
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.
Mennerick
Steven
S
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA. menneris@psychiatry.wustl.edu.
Chisari
Mariangela
M
Shu
Hong-Jin
HJ
Taylor
Amanda
A
Vasek
Michael
M
Eisenman
Lawrence N
LN
Zorumski
Charles F
CF
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry / Q000494:pharmacology*; D018682:GABA Agents / Q000737:chemistry / Q000494:pharmacology*; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009865:Oocytes; D018408:Patch-Clamp Techniques; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D013194:Staining and Labeling / Q000379:methods*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D056969:Voltage-Sensitive Dye Imaging / Q000379:methods*; D014982:Xenopus laevis
D005456:Fluorescent Dyes; D018682:GABA Agents; D018755:GABA Agonists; D018756:GABA Antagonists; D011963:Receptors, GABA-A