Diverse Voltage-Sensitive Dyes Modulate GABAAReceptor 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 GABAA receptor with maximum efficacy and potency similar to clinically used GABAA 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 GABAA 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 GABAA receptor function. Even dyes with no activity on GABAA receptors at baseline induced photodynamic enhancement of GABAA 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 year

  2010

• Venue

  Journal of Neuroscience

• Publication date

  2010-02-24

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1523/JNEUROSCI.5607-09.2010PMID 20181584PMCID PMC2840391
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The influence of neuroactive steroid lipophilicity on GABAA receptor modulation: evidence for a low-affinity interaction.

  2009cited by this paper
• Effect of voltage sensitive fluorescent proteins on neuronal excitability.

  2009cited by this paper
• Electrophysiology in the age of light

  2009cited by this paper
• Photodynamic Effects of Steroid-Conjugated Fluorophores on GABAA Receptors

  2009cited by this paper
• Anesthetic-Like Modulation of Receptor Function by Surfactants: A Test of the Interfacial Theory of Anesthesia

  2008cited by this paper
• High-Speed Imaging Reveals Neurophysiological Links to Behavior in an Animal Model of Depression

  2007cited by this paper
• ANNINE-6plus, a voltage-sensitive dye with good solubility, strong membrane binding and high sensitivity

  2007cited by this paper
• Voltage-Sensitive Oxonol Dyes Are Novel Large-Conductance Ca2+-Activated K+ Channel Activators Selective for β1 and β4 but Not for β2 Subunits

  2007influential reference
• Anticonvulsant and anesthetic effects of a fluorescent neurosteroid analog activated by visible light

  2007influential reference
• Optical and electrophysiological recordings of corticospinal synaptic activity and its developmental change in in vitro rat slice co-cultures.

  2007cited by this paper
• Voltage-sensitive oxonol dyes are novel large-conductance Ca2+-activated K+ channel activators selective for beta1 and beta4 but not for beta2 subunits.

  2007influential reference
• GABA(A) receptor function is regulated by lipid bilayer elasticity.

  2006cited by this paper
• An extremely rich repertoire of bursting patterns during the development of cortical cultures

  2006influential reference
• GABAA receptor function is regulated by lipid bilayer elasticity

  2006cited by this paper
• Imaging membrane potential in dendrites and axons of single neurons

  2006cited by this paper
• Neurosteroid Access to the GABAA Receptor

  2005cited by this paper
• IL-13受体α2降低血吸虫病肉芽肿的炎症反应并延长宿主存活时间[英]/Mentink-Kane MM,Cheever AW，Thompson RW，et al//Proc Natl Acad Sci U S A

  2005cited by this paper
• Emerging molecular mechanisms of general anesthetic action.

  2005cited by this paper
• How lipophilic cannabinergic ligands reach their receptor sites.

  2005cited by this paper
• Purkinje cell functions in the in vitro cerebellum isolated from neonatal rats in a block with the pons and medulla.

  2004cited by this paper
• Slow Actions of Neuroactive Steroids at GABAA Receptors

  2004cited by this paper
• VSDI: a new era in functional imaging of cortical dynamics

  2004cited by this paper
• Spatiotemporal Dynamics of Sensory Responses in Layer 2/3 of Rat Barrel Cortex Measured In Vivo by Voltage-Sensitive Dye Imaging Combined with Whole-Cell Voltage Recordings and Neuron Reconstructions

  2003cited by this paper
• Reversible modulation of GABAA receptor‐mediated currents by light is dependent on the redox state of the receptor

  2003cited by this paper
• Spatio-temporal dynamics of odor representations in the mammalian olfactory bulb.

  2002cited by this paper
• A new approach to neural cell culture for long-term studies.

  2001cited by this paper
• Positive allosteric modulation by ultraviolet irradiation on GABAA, but not GABAC, receptors expressed in Xenopus oocytes

  2001cited by this paper
• Quantification of optical signals with electrophysiological signals in neural activities of Di-4-ANEPPS stained rat hippocampal slices.

  2000cited by this paper
• Cortex-restricted disruption of NMDAR1 impairs neuronal patterns in the barrel cortex

  2000cited by this paper
• Presynaptic Inhibition of Primary Olfactory Afferents Mediated by Different Mechanisms in Lobster and Turtle

  1999cited by this paper
• Fast optical recordings of membrane potential changes from dendrites of pyramidal neurons.

  1999cited by this paper
• Imaging Cortical Dynamics at High Neurotechnique Spatial and Temporal Resolution with Novel Blue Voltage-Sensitive Dyes

  1999cited by this paper
• Functional study of the rat cortical microcircuitry with voltage-sensitive dye imaging of neocortical slices.

  1997cited by this paper
• Voltage sensing by fluorescence resonance energy transfer in single cells.

  1995cited by this paper
• Passive and synaptic properties of hippocampal neurons grown in microcultures and in mass cultures.

  1995influential reference
• Susceptibility of cloned K+ channels to reactive oxygen species.

  1995cited by this paper
• Characterization of impulse propagation at the microscopic level across geometrically defined expansions of excitable tissue: multiple site optical recording of transmembrane voltage (MSORTV) in patterned growth heart cell cultures

  1994cited by this paper
• Multiple site optical recording of transmembrane voltage (MSORTV) in patterned growth heart cell cultures: assessing electrical behavior, with microsecond resolution, on a cellular and subcellular scale.

  1994influential reference
• Mechanisms of rapid optical changes of potential sensitive dyes.

  1977cited by this paper
• Internal and external application of photodynamic sensitizers on squid giant axons

  1977cited by this paper

• Imaging of Evoked Cortical Depolarizations Using Either ASAP2s, or chi-VSFP, or Di-4-Anepps, or Autofluorescence Optical Signals.

  2023cites this paper
• Compact Electrochromic Optical Recording of Bioelectric Potentials

  2023cites this paper
• A review on 3D printing functional brain model

  2022cites this paper
• Dual-Color Optical Recording of Bioelectric Potentials by Polymer Electrochromism

  2022cites this paper
• Establishment of a high throughput screening system for GABAA1 modulators in living cells.

  2022cites this paper
• AgNPs reduce reproductive capability of female mouse for their toxic effects on mouse early embryo development

  2022cites this paper
• Optical Electrophysiology: Toward the Goal of Label-Free Voltage Imaging.

  2021cites this paper
• Studying Synaptically Evoked Cortical Responses ex vivo With Combination of a Single Neuron Recording (Whole-Cell) and Population Voltage Imaging (Genetically Encoded Voltage Indicator)

  2021cites this paper
• Voltage-Sensitive Dye versus Intrinsic Signal Optical Imaging: Comparison of Tactile Responses in Primary and Secondary Somatosensory Cortices of Rats

  2021cites this paper
• A novel fluorescence probe based on specific recognition of GABAA receptor for imaging cell membrane.

  2020cites this paper
• Voltage Imaging of Cortical Oscillations in Layer 1 with Two-Photon Microscopy

  2020influential citation
• Optical Imaging of Electrical and Mechanical Couplings between Cells.

  2020cites this paper
• The impact of two autism related genes on amygdala physiology

  2019cites this paper
• Primer to Voltage Imaging With ANNINE Dyes and Two-Photon Microscopy

  2019cites this paper
• Technologies to Study Action Potential Propagation With a Focus on HD-MEAs

  2019cites this paper
• Construction of a Fluorescent Screening System of Allosteric Modulators for the GABAA Receptor Using a Turn-On Probe

  2019cites this paper
• Membrane water for probing neuronal membrane potentials and ionic fluxes at the single cell level

  2018cites this paper
• Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission

  2018cites this paper
• Characterization of di-4-ANEPPS with nano-black lipid membranes.

  2018cites this paper
• Positive allosteric modulation of GABAA receptors in the amygdala, hippocampus and thalamocortical circuits by XBD173, diazepam and allopregnanolone: a comparative VSDI study

  2018influential citation
• Optical Imaging With Voltage Sensors—Capturing TMS-Induced Neuronal Signals Using Light

  2018cites this paper
• Nonlinear microscopy for temporally and spatially resolved label-free imaging of living cells

  2018cites this paper
• Advances and Current Challenges Associated with the Use of Human Induced Pluripotent Stem Cells in Modeling Neurodegenerative Disease

  2018influential citation
• Breaking the Excitation-Inhibition Balance Makes the Cortical Network's Space-Time Dynamics Distinguish Simple Visual Scenes

  2017cites this paper
• Continuous multimodality brain imaging reveals modified neurovascular seizure response after intervention

  2017cites this paper
• Voltage Imaging: Pitfalls and Potential.

  2017cites this paper
• Continuous multi-modality brain imaging reveals modified neurovascular seizure response after intervention.

  2017cites this paper
• Rapid Throughput Analysis of GABAA Receptor Subtype Modulators and Blockers Using DiSBAC1(3) Membrane Potential Red Dye

  2017influential citation
• Catching the voltage gradient—asymmetric boost of cortical spread generates motion signals across visual cortex: a brief review with special thanks to Amiram Grinvald

  2017cites this paper
• Quantum Dot-Peptide-Fullerene Bioconjugates for Visualization of in Vitro and in Vivo Cellular Membrane Potential.

  2017cites this paper
• Effects of GABAA kinetics on cortical population activity: computational studies and physiological confirmations.

  2016influential citation
• Layer-specific potentiation of network GABAergic inhibition in the CA1 area of the hippocampus

  2016cites this paper
• Chemical and Biochemical Sensors, 1. Fundamentals

  2016cites this paper
• Flexibility in the nervous system: Regulation of axonal spike initiation in a sensory neuron fine-tunes signal integration

  2016cites this paper
• Voltage imaging to understand connections and functions of neuronal circuits.

  2016cites this paper
• Route to genetically targeted optical electrophysiology: development and applications of voltage-sensitive fluorescent proteins

  2015cites this paper
• Quantification of bursting and synchrony in cultured hippocampal neurons.

  2015cites this paper
• Imaging the Awake Visual Cortex with a Genetically Encoded Voltage Indicator

  2015cites this paper
• Interaction between positive allosteric modulators and trapping blockers of the NMDA receptor channel

  2015cites this paper
• Comparative performance of a genetically-encoded voltage indicator and a blue voltage sensitive dye for large scale cortical voltage imaging

  2015cites this paper
• High-Speed imaging reveals opposing effects of chronic stress and antidepressants on neuronal activity propagation through the hippocampal trisynaptic circuit

  2015cites this paper
• Modulation of NMDA Receptor Activity During Physiological and Pathophysiological Events

  2014influential citation
• Purinergic control of hippocampal circuit hyperexcitability in Dravet syndrome

  2014cites this paper
• Fluorescent Indicators for Functional Optical Imaging

  2014cites this paper
• Processing Submillisecond Timing Differences in a Model Electrosensory System

  2014cites this paper
• A methodology for fast assessments to the electrical activity of barrel fields in vivo: from population inputs to single unit outputs

  2014cites this paper
• Optical Imaging of Neuronal Activity and Visualization of Fine Neural Structures in Non-Desheathed Nervous Systems

  2014cites this paper
• High-resolution spatio-temporal bioactivity of a novel peptide revealed by optical imaging in rat orbitofrontal cortex in vitro: possible implications for neurodegenerative diseases.

  2013cites this paper
• Comparison of Two Voltage-Sensitive Dyes and Their Suitability for Long-Term Imaging of Neuronal Activity

  2013cites this paper
• Endogenous voltage gradients as mediators of cell-cell communication: strategies for investigating bioelectrical signals during pattern formation

  2013cites this paper
• Indistinguishable Synaptic Pharmacodynamics of the N-Methyl-d-Aspartate Receptor Channel Blockers Memantine and Ketamine

  2013cites this paper
• Retrograde Fluorescent Labeling Allows for Targeted Extracellular Single-unit Recording from Identified Neurons In vivo

  2013cites this paper
• Modulation of synaptic plasticity by the coactivation of spatially distinct synaptic inputs in rat hippocampal CA1 apical dendrites.

  2013cites this paper
• Optogenetic approaches for functional mouse brain mapping

  2013cites this paper
• Yellow Fluorescent Protein-Based Assay to Measure GABAA Channel Activation and Allosteric Modulation in CHO-K1 Cells

  2013cites this paper
• Cardiac action potential imaging

  2013cites this paper
• The voltage-sensitive dye di-4-ANEPPS slows conduction velocity in isolated guinea pig hearts.

  2012cites this paper
• An evaluation of in vivo voltage-sensitive dyes: pharmacological side effects and signal-to-noise ratios after effective removal of brain-pulsation artifacts.

  2012cites this paper
• Two-Photon Compatibility and Single-Voxel, Single-Trial Detection of Subthreshold Neuronal Activity by a Two-Component Optical Voltage Sensor

  2012cites this paper
• β-Adrenergic modulation of spontaneous spatiotemporal activity patterns and synchrony in hyperexcitable hippocampal circuits.

  2012cites this paper
• Molecular bioelectricity in developmental biology: New tools and recent discoveries

  2012cites this paper
• Source separation analysis of visual cortical dynamics revealed by voltage sensitive dye imaging

  2012cites this paper
• Entorhinal theta-frequency input to the dentate gyrus trisynaptically evokes hippocampal CA1 LTP

  2012cites this paper
• Synaptic NMDA Receptors Mediate Hypoxic Excitotoxic Death

  2012cites this paper
• Variable Neuronal Participation in Stereotypic Motor Programs

  2012cites this paper
• General principles for measuring resting membrane potential and ion concentration using fluorescent bioelectricity reporters.

  2012cites this paper
• Synchronization analysis of voltage-sensitive dye imaging during focal seizures in the rat neocortex.

  2011cites this paper
• Two-photon imaging and analysis of neural network dynamics

  2011cites this paper
• Development of a non-linear optical microscope for real-time measurement of neuronal activity in sub-micrometric structures

  2011cites this paper
• Human Pluripotent Stem Cell-Derived Neuronal Networks:Their Electrical Functionality and Usability for Modelling and Toxicology

  2011cites this paper
• Dendritic integration in hippocampal dentate gyrus granule cells

  2011cites this paper
• Neuron Primer Imaging Voltage in Neurons

  2011cites this paper
• High Precision and Fast Functional Mapping of Brain Circuitry through Laser Scanning Photostimulation and Fast Dye Imaging

  2011cites this paper
• Study of the vesicular cycle in nerve structures in somatic muscle of earthworm (Lumbricus terrestris)

  2011influential citation
• GABAA receptor-mediated modulation of neuronal activity propagation upon tetanic stimulation in rat hippocampal slices

  2010cites this paper
• Imaging brain electric signals with genetically targeted voltage-sensitive fluorescent proteins

  2010cites this paper
• Integration of Synchronous Input in Dentate Granule Cells ... Integration of Synchronous Input in Dentate Granule Cells ..... Clustered Input Is Integrated Linearly with a Gain

  year unknowncites this paper
• Frontiers in Cellular Neuroscience Cellular Neuroscience

  year unknowncites this paper