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Design and Use of Organic Voltage Sensitive Dyes

  • Chapter
Membrane Potential Imaging in the Nervous System and Heart

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 859))

Abstract

The chemistry and the physics of voltage sensitive dyes (VSDs) should be understood and appreciated as a prerequisite for their optimal application to problems in neuroscience cardiology. This chapter provides a basic understanding of the properties of the large variety of available organic VSDs. The mechanisms by which the dyes respond to voltage guides the best set up of the optics for recording or imaging electrophysiological activity. The physical and chemical properties of the dyes can be tuned to optimize delivery to and staining of the cells in different experimental preparations. The aim of this chapter is to arm the experimentalists who use the dyes with enough information and data to be able to intelligently choose the best dye for their specific requirements.

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References

  • Acker CD, Loew LM (2013) Characterization of voltage-sensitive dyes in living cells using two-photon excitation. Methods Mol Biol 995:147–160

    CAS  PubMed  Google Scholar 

  • Acker CD, Yan P, Loew LM (2011) Single-voxel recording of voltage transients in dendritic spines. Biophys J 101:L11–L13

    CAS  PubMed Central  PubMed  Google Scholar 

  • Akemann W, Mutoh H, Perron A, Rossier J, Knopfel T (2010) Imaging brain electric signals with genetically targeted voltage-sensitive fluorescent proteins. Nat Methods 7:643–649

    CAS  PubMed  Google Scholar 

  • Antic S, Major G, Zecevic D (1999) Fast optical recordings of membrane potential changes from dendrites of pyramidal neurons. J Neurophysiol 82:1615–1621

    CAS  PubMed  Google Scholar 

  • Antic S, Wuskell JP, Loew L, Zecevic D (2000) Functional profile of the giant metacerebral neuron of Helix aspersa: temporal and spatial dynamics of electrical activity in situ. J Physiol 527:55–69

    CAS  PubMed Central  PubMed  Google Scholar 

  • Antic S, Zecevic D (1995) Optical signals from neurons with internally applied voltage-sensitive dyes. J Neurosci 15:1392–1405

    CAS  PubMed  Google Scholar 

  • Antic SD (2003) Action potentials in basal and oblique dendrites of rat neocortical pyramidal neurons. J Physiol (Lond) 550:35–50

    CAS  Google Scholar 

  • Araya R, Jiang J, Eisenthal KB, Yuste R (2006) The spine neck filters membrane potentials. Proc Natl Acad Sci U S A 103:17961–17966

    CAS  PubMed Central  PubMed  Google Scholar 

  • Araya R, Nikolenko V, Eisenthal KB, Yuste R (2007) Sodium channels amplify spine potentials. Proc Natl Acad Sci U S A 104:12347–12352

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ataka K, Pieribone VA (2002) A genetically targetable fluorescent probe of channel gating with rapid kinetics. Biophys J 82:509–516

    CAS  PubMed Central  PubMed  Google Scholar 

  • Baker BJ, Lee H, Pieribone VA, Cohen LB, Isacoff EY, Knopfel T, Kosmidis EK (2007) Three fluorescent protein voltage sensors exhibit low plasma membrane expression in mammalian cells. J Neurosci Methods 161:32–38

    CAS  PubMed  Google Scholar 

  • Beach JM, McGahren ED, Xia J, Duling BR (1996) Ratiometric measurement of endothelial cell depolarization in arterioles with a potential sensitive dye. Am J Physiol 270:H2216–H2227

    CAS  PubMed  Google Scholar 

  • Bedlack RS, Wei M-d, Fox SH, Gross E, Loew LM (1994) Distinct electric potentials in soma and neurite membranes. Neuron 13:1187–1193

    CAS  PubMed  Google Scholar 

  • Bedlack RS, Wei M-d, Loew LM (1992) Localized membrane depolarizations and localized intracellular calcium influx during electric field-guided neurite growth. Neuron 9:393–403

    CAS  PubMed  Google Scholar 

  • Ben-Oren I, Peleg G, Lewis A, Minke B, Loew LM (1996) Infrared nonlinear optical measurements of membrane potential in photoreceptor cells. Biophys J 71:1616–1620

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bouevitch O, Lewis A, Pinevsky I, Wuskell JP, Loew LM (1993) Probing membrane potential with non-linear optics. Biophys J 65:672–679

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bradley J, Luo R, Otis TS, DiGregorio DA (2009) Submillisecond optical reporting of membrane potential in situ using a neuronal tracer dye. J Neurosci 29:9197–9209

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bullen A, Patel SS, Saggau P (1997) High speed random access fluorescence microscopy: I. High resolution optical recording with voltage-sensitive dyes and ion indicators. Biophys J 73:477–491

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bullen A, Saggau P (1999) High-speed, random-access fluorescence microscopy: II. Fast quantitative measurements with voltage-sensitive dyes [in process citation]. Biophys J 76:2272–2287

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cacciatore TW, Brodfuehrer PD, Gonzalez JE, Jiang T, Adams SR, Tsien RY, Kristan WB Jr, Kleinfeld D (1999) Identification of neural circuits by imaging coherent electrical activity with FRET-based dyes. Neuron 23:449–459

    CAS  PubMed  Google Scholar 

  • Campagnola P, Loew LM (2003) Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms. Nat Biotechnol 21:1356–1360

    CAS  PubMed  Google Scholar 

  • Campagnola PJ, Wei M-d, Lewis A, Loew LM (1999) High resolution optical imaging of live cells by second harmonic generation. Biophys J 77:3341–3349

    CAS  PubMed Central  PubMed  Google Scholar 

  • Canepari M, Djurisic M, Zecevic D (2007) Dendritic signals from rat hippocampal CA1 pyramidal neurons during coincident pre- and post-synaptic activity: a combined voltage- and calcium-imaging study. J Physiol 580:463–484

    CAS  PubMed Central  PubMed  Google Scholar 

  • Canepari M, Vogt K, Zecevic D (2008) Combining voltage and calcium imaging from neuronal dendrites. Cell Mol Neurobiol 28(8):1079–1093

    CAS  PubMed Central  PubMed  Google Scholar 

  • Canepari M, Willadt S, Zecevic D, Vogt KE (2010) Imaging inhibitory synaptic potentials using voltage sensitive dyes. Biophys J 98:2032–2040

    CAS  PubMed Central  PubMed  Google Scholar 

  • Clark HA, Campagnola PJ, Wuskell JP, Lewis A, Loew LM (2000) Second harmonic generation properties of fluorescent polymer encapsulated gold nanoparticles. J Am Chem Soc 122:10234–10235

    CAS  Google Scholar 

  • Cohen LB, Salzberg BM, Davila HV, Ross WN, Landowne D, Waggoner AS, Wang CH (1974) Changes in axon fluorescence during activity: molecular probes of membrane potential. J Membr Biol 19:1–36

    CAS  PubMed  Google Scholar 

  • Denk W, Strickler JH, Webb WW (1990) Two-photon laser scanning fluorescence microscopy. Science 248:73–76

    CAS  PubMed  Google Scholar 

  • Derdikman D, Hildesheim R, Ahissar E, Arieli A, Grinvald A (2003) Imaging spatiotemporal dynamics of surround inhibition in the barrels somatosensory cortex. J Neurosci 23:3100–3105

    CAS  PubMed  Google Scholar 

  • Djurisic M, Zecevic D (2005) Imaging of spiking and subthreshold activity of mitral cells with voltage-sensitive dyes. Ann N Y Acad Sci 1048:92–102

    PubMed  Google Scholar 

  • Djurisic M, Zochowski M, Wachowiak M, Falk CX, Cohen LB, Zecevic D (2003) Optical monitoring of neural activity using voltage-sensitive dyes. Methods Enzymol 361:423–451

    CAS  PubMed  Google Scholar 

  • Dombeck DA, Blanchard-Desce M, Webb WW (2004) Optical recording of action potentials with second-harmonic generation microscopy. J Neurosci 24:999–1003

    CAS  PubMed  Google Scholar 

  • Dombeck DA, Sacconi L, Blanchard-Desce M, Webb WW (2005) Optical recording of fast neuronal membrane potential transients in acute mammalian brain slices by second-harmonic generation microscopy. J Neurophysiol 94:3628–3636

    PubMed  Google Scholar 

  • Dragsten PR, Webb WW (1978) Mechanism of the membrane potential sensitivity of the fluorescent membrane probe merocyanine 540. Biochemistry 17:5228–5240

    CAS  PubMed  Google Scholar 

  • Efimov IR, Nikolski VP, Salama G (2004) Optical imaging of the heart. Circ Res 95:21–33

    CAS  PubMed  Google Scholar 

  • Ehrenberg B, Montana V, Wei M-d, Wuskell JP, Loew LM (1988) Membrane potential can be determined in individual cells from the Nernstian distribution of cationic dyes. Biophys J 53:785–794

    CAS  PubMed Central  PubMed  Google Scholar 

  • Farkas DL, Wei M, Febbroriello P, Carson JH, Loew LM (1989) Simultaneous imaging of cell and mitochondrial membrane potential. Biophys J 56:1053–1069

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fedorov VV, Ambrosi CM, Kostecki G, Hucker WJ, Glukhov AV, Wuskell JP, Loew LM, Moazami N, Efimov IR (2011) Anatomic localization and autonomic modulation of atrioventricular junctional rhythm in failing human hearts. Circ Arrhythm Electrophysiol 4:515–525

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fedorov VV, Glukhov AV, Chang R, Kostecki G, Aferol H, Hucker WJ, Wuskell JP, Loew LM, Schuessler RB, Moazami N, Efimov IR (2010) Optical mapping of the isolated coronary-perfused human sinus node. J Am Coll Cardiol 56:1386–1394

    PubMed Central  PubMed  Google Scholar 

  • Fink AE, Bender KJ, Trussell LO, Otis TS, DiGregorio DA (2012) Two-photon compatibility and single-voxel, single-trial detection of subthreshold neuronal activity by a two-component optical voltage sensor. PLoS One 7, e41434

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fisher JAN, Barchi JR, Welle CG, Kim G-H, Kosterin P, Obaid AL, Yodh AG, Contreras D, Salzberg BM (2008) Two-photon excitation of potentiometric probes enables optical recording of action potentials from mammalian nerve terminals in Situ. J Neurophysiol 99:1545–1553

    PubMed  Google Scholar 

  • Fluhler E, Burnham VG, Loew LM (1985) Spectra, membrane binding and potentiometric responses of new charge shift probes. Biochemistry 24:5749–5755

    CAS  PubMed  Google Scholar 

  • Foust A, Popovic M, Zecevic D, McCormick DA (2010) Action potentials initiate in the axon initial segment and propagate through axon collaterals reliably in cerebellar purkinje neurons. J Neurosci 30:6891–6902

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fromherz P, Hubener G, Kuhn B, Hinner MJ (2008) ANNINE-6plus, a voltage-sensitive dye with good solubility, strong membrane binding and high sensitivity. Eur Biophys J 37:509–514

    CAS  PubMed Central  PubMed  Google Scholar 

  • Glover JC, Sato K, Momose-Sato Y (2008) Using voltage-sensitive dye recording to image the functional development of neuronal circuits in vertebrate embryos. Dev Neurobiol 68:804–816

    PubMed  Google Scholar 

  • Gong Y, Wagner MJ, Zhong Li J, Schnitzer MJ (2014) Imaging neural spiking in brain tissue using FRET-opsin protein voltage sensors. Nat Commun 5:3674

    PubMed Central  PubMed  Google Scholar 

  • Gonzalez JE, Tsien RY (1995) Voltage sensing by fluorescence resonance energy transfer in single cells. Biophys J 69:1272–1280

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gonzalez JE, Tsien RY (1997) Improved indicators of membrane potential that use fluorescence resonance energy transfer. Chem Biol 4:269–277

    CAS  PubMed  Google Scholar 

  • Grinvald A, Hildesheim R (2004) VSDI: a new era in functional imaging of cortical dynamics. Nat Rev Neurosci 5:874–885

    CAS  PubMed  Google Scholar 

  • Gross E, Bedlack RS, Loew LM (1994) Dual-wavelength ratiometric measurement of the membrane dipole potential. Biophys J 67:208–216

    CAS  PubMed Central  PubMed  Google Scholar 

  • Guerrero G, Siegel MS, Roska B, Loots E, Isacoff EY (2002) Tuning FlaSh: redesign of the dynamics, voltage range, and color of the genetically encoded optical sensor of membrane potential. Biophys J 83:3607–3618

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gupta RK, Salzberg BM, Grinvald A, Cohen LB, Kamino K, Lesher S, Boyle MB, Waggoner AS, Wang C (1981) Improvements in optical methods for measuring rapid changes in membrane potential. J Membr Biol 58:123–137

    CAS  PubMed  Google Scholar 

  • Habib ERMS, Komuro R, Yan P, Hayashi S, Inaji M, Momose-Sato Y, Loew LM, Sato K (2013) Evaluation of voltage-sensitive fluorescence dyes for monitoring neuronal activity in the embryonic central nervous system. J Membr Biol 246:679–688

    Google Scholar 

  • Hochbaum DR, Zhao Y, Farhi SL, Klapoetke N, Werley CA, Kapoor V, Zou P, Kralj JM, Maclaurin D, Smedemark-Margulies N, Saulnier JL, Boulting GL, Straub C, Cho YK, Melkonian M, Wong GK, Harrison DJ, Murthy VN, Sabatini BL, Boyden ES, Campbell RE, Cohen AE (2014) All-optical electrophysiology in mammalian neurons using engineered microbial rhodopsins. Nat Methods 11(8):825–833

    CAS  PubMed Central  PubMed  Google Scholar 

  • Holthoff K, Zecevic D, Konnerth A (2010) Rapid time course of action potentials in spines and remote dendrites of mouse visual cortex neurons. J Physiol 588:1085–1096

    CAS  PubMed Central  PubMed  Google Scholar 

  • Huang JY, Lewis A, Loew LM (1988) Non-linear optical properties of potential sensitive styryl dyes. Biophys J 53:665–670

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jiang J, Eisenthal KB, Yuste R (2007) Second harmonic generation in neurons: electro-optic mechanism of membrane potential sensitivity. Biophys J 93:L26–L28

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jin L, Han Z, Platisa J, Wooltorton JRA, Cohen LB, Pieribone VA (2012) Single action potentials and subthreshold electrical events imaged in neurons with a fluorescent protein voltage probe. Neuron 75:779–785

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kampa BM, Stuart GJ (2006) Calcium spikes in basal dendrites of layer 5 pyramidal neurons during action potential bursts. J Neurosci 26:7424–7432

    CAS  PubMed  Google Scholar 

  • Kee MZ, Wuskell JP, Loew LM, Augustine GJ, Sekino Y (2008) Imaging activity of neuronal populations with new long-wavelength voltage-sensitive dyes. Brain Cell Biol 36:57–72

    Google Scholar 

  • Knisley SB, Justice RK, Kong W, Johnson PL (2000) Ratiometry of transmembrane voltage-sensitive fluorescent dye emission in hearts. Am J Physiol Heart Circ Physiol 279:H1421–H1433

    CAS  PubMed  Google Scholar 

  • Kralj JM, Hochbaum DR, Douglass AD, Cohen AE (2011) Electrical spiking in escherichia coli probed with a fluorescent voltage-indicating protein. Science 333:345–348

    CAS  PubMed  Google Scholar 

  • Kuhn B, Denk W, Bruno RM (2008) In vivo two-photon voltage-sensitive dye imaging reveals top-down control of cortical layers 1 and 2 during wakefulness. Proc Natl Acad Sci U S A 105:7588–7593

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kuhn B, Fromherz P (2003) Anellated hemicyanine dyes in a neuron membrane: molecular Stark effect and optical voltage recording. J Phys Chem B 107:7903–7913

    CAS  Google Scholar 

  • Kuhn B, Fromherz P, Denk W (2004) High sensitivity of stark-shift voltage-sensing dyes by one- or two-photon excitation near the red spectral edge. Biophys J 87:631–639

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lee P, Bollensdorff C, Quinn TA, Wuskell JP, Loew LM, Kohl P (2011) Single-sensor system for spatially-resolved, continuous and multi-parametric optical mapping of cardiac tissue. Heart Rhythm 8:1482–1491

    PubMed Central  PubMed  Google Scholar 

  • Lee P, Taghavi F, Yan P, Ewart P, Ashley EA, Loew LM, Kohl P, Bollensdorff C, Woods CE (2012a) In situ optical mapping of voltage and calcium in the heart. PLoS One 7, e42562

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lee P, Wang K, Woods CE, Yan P, Kohl P, Ewart P, Loew LM, Terrar DA, Bollensdorff C (2012b) Cardiac electrophysiological imaging systems scalable for high-throughput drug testing. Pflugers Arch 464:645–656

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lee P, Yan P, Ewart P, Kohl P, Loew LM, Bollensdorff C (2012c) Simultaneous measurement and modulation of multiple physiological parameters in the isolated heart using optical techniques. Pflugers Arch 464:403–414

    CAS  PubMed Central  PubMed  Google Scholar 

  • Loew LM (1993) Confocal microscopy of potentiometric fluorescent dyes. Methods Cell Biol 38:194–209

    Google Scholar 

  • Loew LM (1994) Voltage sensitive dyes and imaging neuronal activity. Neuroprotocols 5:72–79

    CAS  Google Scholar 

  • Loew LM (2001) Mechanisms and principles of voltage sensitive fluorescence. In: Rosenbaum DS, Jalife J (eds) Optical mapping of cardiac excitation and arrhythmias. Futura Publishing, Armonk, NY, pp 33–46

    Google Scholar 

  • Loew LM, Bonneville GW, Surow J (1978) Charge shift optical probes of membrane potential. Theory. Biochemistry 17:4065–4071

    CAS  PubMed  Google Scholar 

  • Loew LM, Campagnola P, Lewis A, Wuskell JP (2002) Confocal and nonlinear optical imaging of potentiometric dyes. Methods Cell Biol 70:429–452

    CAS  PubMed  Google Scholar 

  • Loew LM, Cohen LB, Dix J, Fluhler EN, Montana V, Salama G, Wu J-Y (1992) A naphthyl analog of the aminostyryl pyridinium class of potentiometric membrane dyes shows consistent sensitivity in a variety of tissue, cell, and model membrane preparations. J Membr Biol 130:1–10

    CAS  PubMed  Google Scholar 

  • Loew LM, Rosenberg I, Bridge M, Gitler C (1983) Diffusion potential cascade. Convenient detection of transferable membrane pores. Biochemistry 22:837–844

    CAS  PubMed  Google Scholar 

  • Loew LM, Scully S, Simpson L, Waggoner AS (1979a) Evidence for a charge-shift electrochromic mechanism in a probe of membrane potential. Nature 281:497–499

    CAS  PubMed  Google Scholar 

  • Loew LM, Simpson L (1981) Charge shift probes of membrane potential. A probable electrochromic mechanism for ASP probes on a hemispherical lipid bilayer. Biophys J 34:353–365

    CAS  PubMed Central  PubMed  Google Scholar 

  • Loew LM, Simpson L, Hassner A, Alexanian V (1979b) An unexpected blue shift caused by differential solvation of a chromophore oriented in a lipid bilayer. J Am Chem Soc 101:5439–5440

    CAS  Google Scholar 

  • Lojewska Z, Loew LM (1987) Insertion of amphiphilic molecules into membranes is catalyzed by a high molecular weight non-ionic surfactant. Biochim Biophys Acta 899:104–112

    CAS  PubMed  Google Scholar 

  • Matiukas A, Mitrea BG, Pertsov AM, Wuskell JP, Wei MD, Watras J, Millard AC, Loew LM (2006) New near-infrared optical probes of cardiac electrical activity. Am J Physiol Heart Circ Physiol 290:H2633–H2643

    CAS  PubMed  Google Scholar 

  • Matiukas A, Mitrea BG, Qin M, Pertsov AM, Shvedko AG, Warren MD, Zaitsev AV, Wuskell JP, Wei M-d, Watras J, Loew LM (2007) Near infrared voltage sensitive fluorescent dyes optimized for optical mapping in blood-perfused myocardium. Heart Rhythm 4:1441–1451

    PubMed Central  PubMed  Google Scholar 

  • Millard AC, Campagnola PJ, Mohler W, Lewis A, Loew LM (2003a) Second harmonic imaging microscopy. In: Marriott G, Parker I (eds) Methods in enzymology, vol. 361B. Academic, San Diego, pp 47–69

    Google Scholar 

  • Millard AC, Jin L, Lewis A, Loew LM (2003b) Direct measurement of the voltage sensitivity of second-harmonic generation from a membrane dye in patch-clamped cells. Opt Lett 28:1221–1223

    CAS  PubMed  Google Scholar 

  • Millard AC, Jin L, Wei M-d, Wuskell JP, Lewis A, Loew LM (2004) Sensitivity of second harmonic generation from styryl dyes to trans-membrane potential. Biophys J 86:1169–1176

    CAS  PubMed Central  PubMed  Google Scholar 

  • Millard AC, Jin L, Wuskell JP, Boudreau DM, Lewis A, Loew LM (2005a) Wavelength- and time-dependence of potentiometric non-linear optical signals from styryl dyes. J Membr Biol 208:103–111

    CAS  PubMed  Google Scholar 

  • Millard AC, Lewis A, Loew LM (2005b) Second harmonic imaging of membrane potential. In: Yuste R, Konnerth A (eds) Imaging in neuroscience and development. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 463–474

    Google Scholar 

  • Miller EW, Lin JY, Frady EP, Steinbach PA, Kristan WB, Tsien RY (2012) Optically monitoring voltage in neurons by photo-induced electron transfer through molecular wires. Proc Natl Acad Sci U S A 109:2114–2119

    CAS  PubMed Central  PubMed  Google Scholar 

  • Milojkovic BA, Wuskell JP, Loew LM, Antic SD (2005) Initiation of sodium spikelets in basal dendrites of neocortical pyramidal neurons. J Membr Biol 208:155–169

    CAS  PubMed  Google Scholar 

  • Montana V, Farkas DL, Loew LM (1989) Dual wavelength ratiometric fluorescence measurements of membrane potential. Biochemistry 28:4536–4539

    CAS  PubMed  Google Scholar 

  • Nishiyama M, von Schimmelmann MJ, Togashi K, Findley WM, Hong K (2008) Membrane potential shifts caused by diffusible guidance signals direct growth-cone turning. Nat Neurosci 11:762–771

    CAS  PubMed  Google Scholar 

  • Nuriya M, Jiang J, Nemet B, Eisenthal KB, Yuste R (2006) Imaging membrane potential in dendritic spines. Proc Natl Acad Sci U S A 103:786–790

    CAS  PubMed Central  PubMed  Google Scholar 

  • Obaid AL, Loew LM, Wuskell JP, Salzberg BM (2004) Novel naphthylstyryl-pyridinium potentiometric dyes offer advantages for neural network analysis. J Neurosci Methods 134:179–190

    CAS  PubMed  Google Scholar 

  • Palmer LM, Stuart GJ (2009) Membrane potential changes in dendritic spines during action potentials and synaptic input. J Neurosci 29:6897–6903

    CAS  PubMed  Google Scholar 

  • Pons T, Moreaux L, Mongin O, Blanchard-Desce M, Mertz J (2003) Mechanisms of membrane potential sensing with second-harmonic generation microscopy. J Biomed Opt 8:428–431

    CAS  PubMed  Google Scholar 

  • Popovic MA, Gao X, Carnevale NT, Zecevic D (2014) Cortical dendritic spine heads are not electrically isolated by the spine neck from membrane potential signals in parent dendrites. Cereb Cortex 24:385–395

    PubMed Central  PubMed  Google Scholar 

  • Ross WN, Salzberg BM, Cohen LB, Grinvald A, Davila HV, Waggoner AS, Wang CH (1977) Changes in absorption, fluorescence, dichroism, and birefringence in stained giant axons: optical measurement of membrane potential. J Membr Biol 33:141–183

    CAS  PubMed  Google Scholar 

  • Sakai R, Repunte-Canonigo V, Raj CD, Knopfel T (2001) Design and characterization of a DNA-encoded, voltage-sensitive fluorescent protein. Eur J Neurosci 13:2314–2318

    CAS  PubMed  Google Scholar 

  • Sasaki S, Yazawa I, Miyakawa N, Mochida H, Shinomiya K, Kamino K, Momose-Sato Y, Sato K (2002) Optical imaging of intrinsic signals induced by peripheral nerve stimulation in the in vivo rat spinal cord. Neuroimage 17:1240–1255

    PubMed  Google Scholar 

  • Shoham D, Glaser DE, Arieli A, Kenet T, Wijnbergen C, Toledo Y, Hildesheim R, Grinvald A (1999) Imaging cortical dynamics at high spatial and temporal resolution with novel blue voltage-sensitive dyes. Neuron 24:791–802

    CAS  PubMed  Google Scholar 

  • Siegel MS, Isacoff EYIN (1997) A genetically encoded optical probe of membrane voltage. Neuron 19:735–741

    CAS  PubMed  Google Scholar 

  • Slovin H, Arieli A, Hildesheim R, Grinvald A (2002) Long-term voltage-sensitive dye imaging reveals cortical dynamics in behaving monkeys. J Neurophysiol 88:3421–3438

    PubMed  Google Scholar 

  • St-Pierre F, Marshall JD, Yang Y, Gong Y, Schnitzer MJ, Lin MZ (2014) High-fidelity optical reporting of neuronal electrical activity with an ultrafast fluorescent voltage sensor. Nat Neurosci 17(6):884–889

    CAS  PubMed Central  PubMed  Google Scholar 

  • Stuart GJ, Palmer LM (2006) Imaging membrane potential in dendrites and axons of single neurons. Pflugers Arch 453:403–410

    CAS  PubMed  Google Scholar 

  • Teisseyre TZ, Millard AC, Yan P, Wuskell JP, Wei M-d, Lewis A, Loew LM (2007) Non-linear optical potentiometric dyes optimized for imaging with 1064 nm light. J Biomed Opt 12:044001

    PubMed  Google Scholar 

  • Tsau Y, Wenner P, O’Donovan MJ, Cohen LB, Loew LM, Wuskell JP (1996) Dye screening and signal-to-noise ratio for retrogradely transported voltage-sensitive dyes. J Neurosci Methods 170:121–129

    Google Scholar 

  • Tsuda S, Kee MZL, Cunha C, Kim J, Yan P, Loew LM, Augustine GJ (2012) Probing the function of neuronal populations: combining micromirror-based optogenetic photostimulation with voltage-sensitive dye imaging. Neurosci Res 75(1):76–81

    PubMed Central  PubMed  Google Scholar 

  • Tsutsui H, Karasawa S, Okamura Y, Miyawaki A (2008) Improving membrane voltage measurements using FRET with new fluorescent proteins. Nat Methods 5:683–685

    CAS  PubMed  Google Scholar 

  • Waggoner AS, Wang CH, Tolles RL (1977) Mechanism of potential-dependent light absorption changes of lipid bilayer membranes in the presence of cyanine and oxonol dyes. J Membr Biol 33:109–140

    CAS  PubMed  Google Scholar 

  • Warren M, Spitzer KW, Steadman BW, Rees TD, Venable PW, Taylor T, Shibayama J, Yan P, Wuskell JP, Loew LM, Zaitsev AV (2010) High precision recording of the action potential in isolated cardiomyocytes using the near-infrared fluorescent dye di-4-ANBDQBS. Am J Physiol Heart Circ Physiol 299:H1271–H1281

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wenner P, Tsau Y, Cohen LB, O’Donovan MJ, Dan Y (1996) Voltage-sensitive dye recording using retrogradely transported dye in the chicken spinal cord: staining and signal characteristics. J Neurosci Methods 170:111–120

    Google Scholar 

  • Wu J-Y, Lam Y-W, Falk C, Cohen LB, Fang J, Loew L, Prechtl JC, Kleinfeld D, Tsau Y (1998) Voltage-sensitive dyes for monitoring multi-neuronal activity in the intact CNS. Histochem J 30:169–187

    CAS  PubMed  Google Scholar 

  • Wuskell JP, Boudreau D, Wei MD, Jin L, Engl R, Chebolu R, Bullen A, Hoffacker KD, Kerimo J, Cohen LB, Zochowski MR, Loew LM (2006) Synthesis, spectra, delivery and potentiometric responses of new styryl dyes with extended spectral ranges. J Neurosci Methods 151:200–215

    PubMed  Google Scholar 

  • Xu C, Loew LM (2003) The effect of asymmetric surface potentials on the intramembrane electric field measured with voltage-sensitive dyes. Biophys J 84:2768–2780

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yan P, Acker CD, Zhou WL, Lee P, Bollensdorff C, Negrean A, Lotti J, Sacconi L, Antic SD, Kohl P, Mansvelder HD, Pavone FS, Loew LM (2012) A palette of fluorinated voltage sensitive hemicyanine dyes. Proc Natl Acad Sci U S A 109:20443–20448

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yan P, Xie A, Wei M-d, Loew LM (2008) Amino(oligo)thiophene-based environmentally sensitive biomembrane chromophores. J Org Chem 73:6587–6594

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zecevic D (1996) Multiple spike-initiation zones in single neurons revealed by voltage-sensitive dyes. Nature 381:322–325

    CAS  PubMed  Google Scholar 

  • Zhou W-L, Yan P, Wuskell JP, Loew LM, Antic SD (2007) Intracellular long wavelength voltage-sensitive dyes for studying the dynamics of action potentials in axons and thin dendrites. J Neurosci Methods 164:225–239

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhou WL, Yan P, Wuskell JP, Loew LM, Antic SD (2008) Dynamics of action potential backpropagation in basal dendrites of prefrontal cortical pyramidal neurons. Eur J Neurosci 27:923–936

    PubMed Central  PubMed  Google Scholar 

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Acknowledgment

I am indebted to the many talented chemists, microscopists and neuroscientists who have collaborated with me and who have carried out much of the research summarized in this chapter. Most notably, I wish to acknowledge my long term collaborators Larry Cohen, Aaron Lewis, Mei-de Wei and Joe Wuskell. The more recent work in my lab has benefited from collaborations with Ping Yan, Corey Acker and Srdjan Antic. This work was supported by NIH EB001963.

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  1. Department of Cell Biology, R. D. Berlin Center for Cell Analysis and Modeling, University of Connecticut Health Center, Farmington, CT, 06030-6406, USA

    Leslie M. Loew

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  1. Leslie M. Loew
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Correspondence to Leslie M. Loew .

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Editors and Affiliations

  1. Laboratoire Interdisciplinaire de Physique, Grenoble, France

    Marco Canepari

  2. Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut, USA

    Dejan Zecevic

  3. L’Institut de rythmologie et mode´lisation cardiaque LIRYC Universite´ de Bordeaux, Bordeaux, France

    Olivier Bernus

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Loew, L.M. (2015). Design and Use of Organic Voltage Sensitive Dyes. In: Canepari, M., Zecevic, D., Bernus, O. (eds) Membrane Potential Imaging in the Nervous System and Heart. Advances in Experimental Medicine and Biology, vol 859. Springer, Cham. https://doi.org/10.1007/978-3-319-17641-3_2

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