Genetically Encoded Protein Sensors of Membrane Potential

  • Lei Jin
  • Hiroki Mutoh
  • Thomas Knopfel
  • Lawrence B. Cohen
  • Thom Hughes
  • Vincent A. Pieribone
  • Ehud Y. Isacoff
  • Brian M. Salzberg
  • Bradley J. Baker
Chapter

Abstract

Organic voltage-sensitive dyes offer very high spatial and temporal resolution for imaging neuronal function. Further progress in imaging activity is expected from the emergent development of genetically encoded fluorescent sensors of membrane potential. These fluorescent protein (FP) voltage sensors overcome some drawbacks of organic voltage sensitive dyes such as non-specificity of cell staining and the low accessibility of the dye to some cell types. In a transgenic animal a genetically encoded sensor could in principle be expressed specifically in any cell type and would have the advantage of staining only the cell population determined by the specificity of the promoter used to drive expression. Challenges remain. First, the response time course of many sensors is slow, with time constants of ∼100 ms. This results in a small fractional fluorescence change, ΔF/F, for action potentials and other brief voltage changes. Second, there are no published reports of attempts to express FP-voltage sensors in transgenic animals. Here we critically review the current status of these developments.

Keywords

Carboxyl Flare Cyan Rhodanine Dipicrylamine 

Notes

Acknowledgments

Supported by NIH grants U24NS057631, DC05259, NS050833, and R21MH064214, and an intramural grant from RIKEN BSI.

References

  1. Akemann W, Lundby A, Mutoh H, Knöpfel T (2009) Effect of voltage sensitive fluorescent proteins on neuronal excitability. Biophys J 96:3959–3976[au3].Google Scholar
  2. Akemann W, Mutoh H, Perron A, Rossier J, Knopfel T (2010) Imaging brain electric signals with genetically targeted voltage-sensitive fluoresent proteins. Nature Methods 10:643–649.Google Scholar
  3. Ataka K, Pieribone VA (2002) A genetically targetable fluorescent probe of channel gating with rapid kinetics. Biophys J 82:509–516.PubMedCrossRefGoogle Scholar
  4. Baird GS, Zacharias DA, Tsien RY (1999) Circular permutation and receptor insertion within green fluorescent proteins. Proc Natl Acad Sci USA 96:11241–11246.PubMedCrossRefGoogle Scholar
  5. Baker BJ, Kosmidis EK et al (2005) Imaging brain activity with voltage- and calcium-sensitive dyes. Cell Mol Neurobiol 25:245–282.PubMedCrossRefGoogle Scholar
  6. Baker BJ, Lee H et al (2007) Three fluorescent protein voltage sensors exhibit low plasma membrane expression in mammalian cells. J Neurosci Meth 161:32–38.CrossRefGoogle Scholar
  7. Blunck R, Chanda B, Bezanilla F (2005) Nano to micro-fluorescence measurements of electric fields in molecules and genetically specified neurons. J Membr Biol 208:91–10.2.PubMedCrossRefGoogle Scholar
  8. Boyden ES, Feng J, Bamberg E, Nagel G, Deisseroth K (2005) Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8:1263–1268.PubMedCrossRefGoogle Scholar
  9. Brown JE, Cohen LB et al (1975) Rapid changes in intracellular free calcium concentration. Detection by metallochromic indicator dyes in squid giant axon. Biophys J 15:1155–1160.PubMedCrossRefGoogle Scholar
  10. 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.PubMedCrossRefGoogle Scholar
  11. Chanda B, Blunck R et al (2005) A hybrid approach to measuring electrical activity in genetically specified neurons. Nat Neurosci 8:1619–1626.PubMedCrossRefGoogle Scholar
  12. Davila HV, Salzberg BM, Cohen LB, Waggoner AS (1973) A large change in axon fluorescence that provides a promising method for measuring membrane potential. Nat New Biol 241:159–160.PubMedGoogle Scholar
  13. DiFranco M, Capote J, Quiñonez M, Vergara JL (2007) Voltage-dependent dynamic FRET signals from the transverse tubules in mammalian skeletal muscle fibers. J Gen Physiol 130:581–600.PubMedCrossRefGoogle Scholar
  14. Dimitrov D, He Y et al (2007) Engineering and characterization of an enhanced fluorescent protein voltage sensor. PLoS ONE 2:e440.PubMedCrossRefGoogle Scholar
  15. Fernández JM, Taylor RE, Bezanilla F (1983) Induced capacitance in the squid giant axon. Lipophilic ion displacement currents. J Gen Physiol 82:331–346.PubMedCrossRefGoogle Scholar
  16. Grinvald A, Hildesheim R (2004) VSDI: a new era in functional imaging of cortical dynamics. Nat Rev Neurosci 5: 874–885.PubMedCrossRefGoogle Scholar
  17. Grinvald A, Hildesheim R, Farber IC, Anglister L (1982) Improved fluorescent probes for the measurement of rapid changes in membrane potential. Biophys J 39:301–308.PubMedCrossRefGoogle Scholar
  18. 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.PubMedCrossRefGoogle Scholar
  19. Hinner MJ, Hübener G, Fromherz P (2006) Genetic targeting of individual cells with a voltage-sensitive dye through enzymatic activation of membrane binding. ChemBioChem 7:495–505.PubMedCrossRefGoogle Scholar
  20. Kalyanaraman B, Feix JB, Sieber F, Thomas JP, Girotti AW (1987) Photodynamic action of merocyanine 540 on artificial and natural cell membranes: involvement of singlet molecular oxygen. Proc Natl Acad Sci USA 84:2999–3003.PubMedCrossRefGoogle Scholar
  21. Knöpfel T, Tomita K, Shimazaki R, Sakai R (2003) Optical recordings of membrane potential using genetically targeted voltage-sensitive fluorescent proteins. Methods 30:42–48.PubMedCrossRefGoogle Scholar
  22. Kohout SC, Ulbrich MH, Bell SC, Isacoff EY (2007) Subunit organization and functional transitions in Ci-VSP. Nat Struct Mol Biol 15:106–108.PubMedCrossRefGoogle Scholar
  23. Loew LM, Cohen LB, Salzberg BM, Obaid AL, Bezanilla F (1985) Charge-shift probes of membrane potential. Characterization of aminostyrylpyridinium dyes on the squid giant axon. Biophys J 47:71–77.PubMedCrossRefGoogle Scholar
  24. Lundby A, Mutoh H, Dimitrov D, Akemann W, Knöpfel T (2008) Engineering of a genetically encodable fluorescent voltage sensor exploiting fast Ci-VSP voltage-sensing movements. PLoS ONE 3:e2514.PubMedCrossRefGoogle Scholar
  25. MacDonald VW, Jobsis FF (1976) Spectrophotometric studies on the pH of frog skeletal muscle. pH change during and after contractile activity. J Gen Physiol 68:179–195.PubMedCrossRefGoogle Scholar
  26. Miesenbock G, Kevrekidis IG (2005) Optical imaging and control of genetically designated neurons in functioning circuits. Ann Rev Neurosci 28:533–563.PubMedCrossRefGoogle Scholar
  27. Murata Y, Iwasaki H, Sasaki M, Inaba K, Okamura Y (2005) Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor. Nature 435:1239–1243.PubMedCrossRefGoogle Scholar
  28. Mutoh H, Perron A et al (2009) Spectrally-resolved response properties of the three most advanced FRET based fluorescent protein voltage probes. PLoS ONE 4:e4555.PubMedCrossRefGoogle Scholar
  29. Nakai J, Ohkura M, Imoto K (2001) A high signal-to-noise Ca2+ probe composed of a single green fluorescent protein. Nat Biotech 19:137–141.CrossRefGoogle Scholar
  30. Perozo E, MacKinnon R, Bezanilla F, Stefani E (1993) Gating currents from a nonconducting mutant reveal open-closed conformations in Shaker K+ channels. Neuron 11:353–358.PubMedCrossRefGoogle Scholar
  31. Ramsey SI, Moran MM, Chong JA, Clapman DE (2006) A voltage-gated proton-selective channel lacking the pore domain. Nature 440:1213–1216.PubMedCrossRefGoogle Scholar
  32. 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.PubMedCrossRefGoogle Scholar
  33. Salzberg BM, Obaid AL, Bezanilla F (1993) Microsecond response of a voltage-sensitive merocyanine dye: fast voltage-clamp measurements on squid giant axon. Japn J Physiol 43 (Suppl 1):S37–S41.Google Scholar
  34. Sasaki M, Takagi M, Okamura Y (2006) A voltage sensor-domain protein is a voltage-gated proton channel. Science 312:589–592.PubMedCrossRefGoogle Scholar
  35. Shimozono S, Miyawaki A (2008) Engineering FRET constructs using CFP and YFP. Meth Cell Biol 85:381–393.CrossRefGoogle Scholar
  36. Siegel MS, Isacoff EY (1997) A genetically encoded optical probe of membrane voltage. Neuron 19:735–741.PubMedCrossRefGoogle Scholar
  37. Sjulson L, Miesenböck G (2007) Optical recording of action potentials and other discrete physiological events: a perspective from signal detection theory. Physiology 22:47–55.PubMedCrossRefGoogle Scholar
  38. Tsien RY (2005) Building and breeding molecules to spy on cells and tumors. FEBS Lett 579:927–932.PubMedCrossRefGoogle Scholar
  39. Tsutsui H, Karasawa S, Okamura Y, Miyawaki A (2008) Improving membrane voltage measurements using FRET with new fluorescent proteins. Nat Methods 8:683–685.CrossRefGoogle Scholar
  40. Villalba-Galea CA, Sandtner W, et al (2009) Charge movement of the voltage sensitive fluorescent protein. Biophys J 96:L19–21.PubMedCrossRefGoogle Scholar
  41. Zecevic D (1996) Multiple spike-initiation zones in single neurons revealed by voltage-sensitive dyes. Nature 381:322–325.PubMedCrossRefGoogle Scholar
  42. Zimmermann D, Kiesel M et al (2008) A combined patch-clamp and electrorotation study of the voltage- and frequency-dependent membrane capacitance caused by structurally dissimilar lipophilic anions. J Membr Biol 22:107–121.Google Scholar
  43. Zochowski M, Wachowiak DM et al (2000) Imaging membrane potential with voltage-sensitive dyes. Biol Bull 198:1–21.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Lei Jin
    • 1
  • Hiroki Mutoh
    • 2
  • Thomas Knopfel
    • 2
  • Lawrence B. Cohen
    • 1
  • Thom Hughes
    • 3
  • Vincent A. Pieribone
    • 1
    • 4
  • Ehud Y. Isacoff
    • 5
  • Brian M. Salzberg
    • 6
  • Bradley J. Baker
    • 1
  1. 1.Department of Cellular and Molecular PhysiologyYale Uniersity School of MedicineNew HavenUSA
  2. 2.Laboratory for Neuronal Circuit DynamicsBrain Science Institute, RIKENSaitamaJapan
  3. 3.Department of Cell Biology and NeuroscienceMontana State UniversityBozemanUSA
  4. 4.John B. Pierce LaboratoryNew HavenUSA
  5. 5.Department of Molecular and Cell BiologyUniversity of CaliforniaBerkleyUSA
  6. 6.Departments of Neurobiology and PhysiologyUniversity of Pennsylvania School of MedicinePhiladelphiaUSA

Personalised recommendations