Wikipedia

Genetically encoded voltage indicator

Genetically encoded voltage indicator (or GEVI) is a protein that can sense membrane potential in a cell and relate the change in voltage to a form of output, often fluorescent level.[1] It is a promising optogenetic recording tool that enables exporting electrophysiological signals from cultured cells, live animals, and ultimately human brain. Examples of notable GEVIs include ArcLight,[2] ASAP1,[3] ASAP3,[4] Archons,[5] SomArchon,[6] and Ace2N-mNeon.[7]

History

edit

Despite that the idea of optical measurement of neuronal activity was proposed in the late 1960s,[8] the first successful GEVI that was convenient enough to put into actual use was not developed until technologies of genetic engineering had become mature in the late 1990s. The first GEVI, coined FlaSh,[9] was constructed by fusing a modified green fluorescent protein with a voltage-sensitive K+ channel (Shaker). Unlike fluorescent proteins, the discovery of new GEVIs were seldom inspired by the nature, for it is hard to find an organism which naturally has the ability to change its fluorescence based on voltage. Therefore, new GEVIs are mostly the products of genetic and protein engineering.

Two methods can be utilized to find novel GEVIs: rational design and directed evolution. The former method contributes to the most of new GEVI variants, but recent researches using directed evolution have shown promising results in GEVI optimization.[10][11]

Structure

edit

GEVI can have many configuration designs in order to realize voltage sensing function.[12] An essential feature of GEVI structure is that it must situate on the cell membrane. Conceptually, the structure of a GEVI should permit the function of sensing the voltage difference and reporting it by change in fluorescence. Usually, the voltage-sensing domain (VSD) of a GEVI spans across the membrane, and is connected to the fluorescent protein(s). However, it is not necessary that sensing and reporting should happen in different structures, e.g. Archons.

By structure, GEVIs can be classified into four categories based on the current findings: (1) GEVIs contain a fluorescent protein FRET pair, e.g. VSFP1, (2) Single opsin GEVIs, e.g. Arch, (3) Opsin-FP FRET pair GEVIs, e.g. MacQ-mCitrine, (4) single FP with special types of voltage sensing domains, e.g. ASAP1. A majority of GEVIs are based on the Ciona intestinalis voltage sensitive phosphatase (Ci-VSP or Ci-VSD (domain)), which was discovered in 2005 from the genomic survey of the organism.[13] Some GEVIs might have similar components, but with different positioning of them. For example, ASAP1 and ArcLight both use a VSD and one FP, but the FP of ASAP1 is on the outside of the cell whereas that of ArcLight is on the inside, and the two FPs of VSFP-Butterfly are separated by the VSD, while the two FPs of Mermaid are relatively close to each other.

Table of GEVIs and their structure
GEVI[A] Year Sensing Reporting Precursor
FlaSh[9] 1997 Shaker (K+ channel) GFP -
VSFP1[14] 2001 Rat Kv2.1 (K+ channel) FRET pair: CFP and YFP -
SPARC[15] 2002 Rat Na+ channel GFP -
VSFP2's[16] 2007 Ci-VSD FRET pair: CFP (Cerulean) and YFP (Citrine) VSFP1
Flare[17] 2007 Kv1.4 (K+ channel) YFP FlaSh
VSFP3.1[18] 2008 Ci-VSD CFP VSFP2's
Mermaid[19] 2008 Ci-VSD FRET pair: Marine GFP (mUKG) and OFP (mKOκ) VSFP2's
hVOS[20] 2008 Dipicrylamine GFP -
Red-shifted VSFP's[21] 2009 Ci-VSD RFP/YFP (Citrine, mOrange2, TagRFP, or mKate2) VSFP3.1
PROPS[22] 2011 Modified green-absorbing proteorhodopsin (GPR) Same as left -
Zahra, Zahra 2[23] 2012 Nv-VSD, Dr-VSD FRET pair: CFP (Cerulean) and YFP (Citrine) VSFP2's
ArcLight[24] 2012 Ci-VSD Modified super ecliptic pHluorin -
Arch[25] 2012 Archaerhodopsin 3 Same as left -
ElectricPk[26] 2012 Ci-VSD Circularly permuted EGFP VSFP3.1
VSFP-Butterfly[27] 2012 Ci-VSD FRET pair: YFP (mCitrine) and RFP (mKate2) VSFP2's
VSFP-CR[28] 2013 Ci-VSD FRET pair: GFP (Clover) and RFP(mRuby2) VSFP2.3
Mermaid2[29] 2013 Ci-VSD FRET pair: CFP (seCFP2) and YFP Mermaid
Mac GEVIs[30] 2014 Mac rhodopsin (FRET acceptor) FRET doner: mCitrine, or mOrange2 -
QuasAr1, QuasAr2[31] 2014 Modified Archaerhodopsin 3 Same as left Arch
Archer[32] 2014 Modified Archaerhodopsin 3 Same as left Arch
ASAP1[3] 2014 Modified Gg-VSD Circularly permuted GFP -
Ace GEVIs[33] 2015 Modified Ace rhodopsin FRET doner: mNeonGreen Mac GEVIs
ArcLightning[34] 2015 Ci-VSD Modified super ecliptic pHluorin ArcLight
Pado[35] 2016 Voltage-gated proton channel Super ecliptic pHluorin -
ASAP2f[36] 2016 Modified Gg-VSD Circularly permuted GFP ASAP1
FlicR1[37] 2016 Ci-VSD Circularly permuted RFP (mApple) VSFP3.1
Bongwoori[38] 2017 Ci-VSD Modified super ecliptic pHluorin ArcLight
ASAP2s[39] 2017 Modified Gg-VSD Circularly permuted GFP ASAP1
ASAP-Y[40] 2017 Modified Gg-VSD Circularly permuted GFP ASAP1
(pa)QuasAr3(-s)[41] 2019 Modified Archaerhodopsin 3 Same as left QuasAr2
Voltron(-ST) 2019 Modified Ace rhodopsin (Ace2) FRET doner: Janelia Fluor (chemical) -
ASAP3[4] 2019 Modified Gg-VSD Circularly permuted GFP ASAP2s
JEDI-2P[42] 2022 Modified Gg-VSD Circularly permuted GFP ASAP2s
  1. ↑Names in italic denote GEVIs not named.

Characteristics

edit

A GEVI can be evaluated by its many characteristics. These traits can be classified into two categories: performance and compatibility. The performance properties include brightness, photostability, sensitivity, kinetics (speed), linearity of response, etc., while the compatibility properties cover toxicity (phototoxicity), plasma membrane localization, adaptability of deep-tissue imaging, etc.[43] For now, no existing GEVI meets all the desired properties, so searching for a perfect GEVI is still a quite competitive research area.

Applications and advantages

edit

Different types of GEVIs are being developed in many biological or physiological research areas. It is thought to be superior to conventional voltage detecting methods like electrode-based electrophysiological recordings, calcium imaging, or voltage sensitive dyes. It has subcellular spatial resolution[44] and temporal resolution as low as 0.2 milliseconds, about an order of magnitude faster than calcium imaging. This allows for spike detection fidelity comparable to electrode-based electrophysiology but without the invasiveness.[33] Researchers have used it to probe neural communications of an intact brain (of Drosophila[45] or mouse[46]), electrical spiking of bacteria (E. coli[22]), and human stem-cell derived cardiomyocyte.[47][48]

Future directions

edit

For GEVI development, its future direction is highly coupled with the target applications. With newer generations of GEVIs overcome the poor performance of the first generation ones, we will see more routes open up for GEVIs to be used in more challenging and versatile applications. Like many other protein biosensors and actuators, once it passes the initial threshold of practicality, there will be more attempts to reshape the tool for its usage in different target applications, each with a different emphasis and requirement for a subset of performance metrics. For example, authors of JEDI-2P stated that the negative-going (bright-to-dim) sensor is good for detecting subthreshold depolarizations and hyperpolarizations but positive-going (dim-to-bright) sensors might be better for spike detection.[42] We may argue that it takes effort to engineer (screen) a perfect sensor, but often the more compelling reason is that simply there is not a unanimous definition of such perfection. For example, scientist might prefer sensors of different emission and excitation colors to be spectrally compatible with other optogenetic actuators. Recently, to compensate for the low signal-to-noise ratio (SNR) due to the poor brightness of GEVI, several denoising methods have been applied to increase SNR.

References

edit
  1. ^ "Genetically-Encoded Voltage Indicators". Openoptogenetics.org. Retrieved 8 May 2017.
  2. ^ Jin, L; Han, Z; Platisa, J; Wooltorton, JR; Cohen, LB; Pieribone, VA (6 September 2012). "Single action potentials and subthreshold electrical events imaged in neurons with a fluorescent protein voltage probe". Neuron. 75 (5): 779–85. doi:10.1016/j.neuron.2012.06.040. PMC 3439164. PMID 22958819.
  3. ^ a b St-Pierre F, Marshall JD, Yang Y, et al. (2014). "High-fidelity optical reporting of neuronal electrical activity with an ultrafast fluorescent voltage sensor". Nat. Neurosci. 17 (6): 884–889. doi:10.1038/nn.3709. PMC 4494739. PMID 24755780.
  4. ^ a b Villette, V; Chavarha, M; Dimov, IK; Bradley, J; Pradhan, L; Mathieu, B; Evans, SW; Chamberland, S; Shi, D; Yang, R; Kim, BB; Ayon, A; Jalil, A; St-Pierre, F; Schnitzer, MJ; Bi, G; Toth, K; Ding, J; Dieudonné, S; Lin, MZ (12 December 2019). "Ultrafast Two-Photon Imaging of a High-Gain Voltage Indicator in Awake Behaving Mice". Cell. 179 (7): 1590–1608.e23. doi:10.1016/j.cell.2019.11.004. PMC 6941988. PMID 31835034.
  5. ^ Piatkevich, Kiryl D.; Jung, Erica E.; Straub, Christoph; Linghu, Changyang; Park, Demian; Suk, Ho-Jun; Hochbaum, Daniel R.; Goodwin, Daniel; Pnevmatikakis, Eftychios; Pak, Nikita; Kawashima, Takashi; Yang, Chao-Tsung; Rhoades, Jeffrey L.; Shemesh, Or; Asano, Shoh; Yoon, Young-Gyu; Freifeld, Limor; Saulnier, Jessica L.; Riegler, Clemens; Engert, Florian; Hughes, Thom; Drobizhev, Mikhail; Szabo, Balint; Ahrens, Misha B.; Flavell, Steven W.; Sabatini, Bernardo L.; Boyden, Edward S. (April 2018). "A robotic multidimensional directed evolution approach applied to fluorescent voltage reporters". Nature Chemical Biology. 14 (4): 352–360. doi:10.1038/s41589-018-0004-9. ISSN 1552-4469. PMC 5866759. PMID 29483642.
  6. ^ Piatkevich, Kiryl D.; Bensussen, Seth; Tseng, Hua-an; Shroff, Sanaya N.; Lopez-Huerta, Violeta Gisselle; Park, Demian; Jung, Erica E.; Shemesh, Or A.; Straub, Christoph; Gritton, Howard J.; Romano, Michael F.; Costa, Emma; Sabatini, Bernardo L.; Fu, Zhanyan; Boyden, Edward S.; Han, Xue (October 2019). "Population imaging of neural activity in awake behaving mice". Nature. 574 (7778): 413–417. Bibcode:2019Natur.574..413P. doi:10.1038/s41586-019-1641-1. ISSN 1476-4687. PMC 6858559. PMID 31597963.
  7. ^ Gong, Y; Huang, C; Li, JZ; Grewe, BF; Zhang, Y; Eismann, S; Schnitzer, MJ (11 December 2015). "High-speed recording of neural spikes in awake mice and flies with a fluorescent voltage sensor". Science. 350 (6266): 1361–6. Bibcode:2015Sci...350.1361G. doi:10.1126/science.aab0810. PMC 4904846. PMID 26586188.
  8. ^ Cohen LB, Keynes RD, Hille B (1968). "Light scattering and birefringence changes during nerve activity". Nature. 218 (5140): 438–441. Bibcode:1968Natur.218..438C. doi:10.1038/218438a0. PMID 5649693. S2CID 4288546.
  9. ^ a b Siegel MS, Isacoff EY (1997). "A genetically encoded optical probe of membrane voltage". Neuron. 19 (4): 735–741. doi:10.1016/S0896-6273(00)80955-1. PMID 9354320.
  10. ^ Piatkevich, Kiryl D.; Jung, Erica E.; Straub, Christoph; Linghu, Changyang; Park, Demian; Suk, Ho-Jun; Hochbaum, Daniel R.; Goodwin, Daniel; Pnevmatikakis, Eftychios; Pak, Nikita; Kawashima, Takashi; Yang, Chao-Tsung; Rhoades, Jeffrey L.; Shemesh, Or; Asano, Shoh; Yoon, Young-Gyu; Freifeld, Limor; Saulnier, Jessica L.; Riegler, Clemens; Engert, Florian; Hughes, Thom; Drobizhev, Mikhail; Szabo, Balint; Ahrens, Misha B.; Flavell, Steven W.; Sabatini, Bernardo L.; Boyden, Edward S. (April 2018). "A robotic multidimensional directed evolution approach applied to fluorescent voltage reporters". Nature Chemical Biology. 14 (4): 352–360. doi:10.1038/s41589-018-0004-9. ISSN 1552-4469. PMC 5866759. PMID 29483642.
  11. ^ Platisa J, Vasan G, Yang A, et al. (2017). "Directed Evolution of Key Residues in Fluorescent Protein Inverses the Polarity of Voltage Sensitivity in the Genetically Encoded Indicator ArcLight". ACS Chem. Neurosci. 8 (3): 513–523. doi:10.1021/acschemneuro.6b00234. PMC 5355904. PMID 28045247.
  12. ^ Gong Y (2015). "The evolving capabilities of rhodopsin-based genetically encoded voltage indicators". Curr. Opin. Chem. Biol. 27: 84–89. doi:10.1016/j.cbpa.2015.05.006. PMC 4571180. PMID 26143170.
  13. ^ Murata Y, Iwasaki H, Sasaki M, et al. (2005). "Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor". Nature. 435 (7046): 1239–1243. Bibcode:2005Natur.435.1239M. doi:10.1038/nature03650. PMID 15902207. S2CID 4427755.
  14. ^ Sakai R, Repunte-Canonigo V, Raj CD, et al. (2001). "Design and characterization of a DNA-encoded, voltage-sensitive fluorescent protein". Eur. J. Neurosci. 13 (12): 2314–2318. doi:10.1046/j.0953-816x.2001.01617.x. PMID 11454036. S2CID 10969720.
  15. ^ Ataka K, Pieribone VA (2002). "A genetically targetable fluorescent probe of channel gating with rapid kinetics". Biophys. J. 82 (1 Pt 1): 509–516. Bibcode:2002BpJ....82..509A. doi:10.1016/S0006-3495(02)75415-5. PMC 1302490. PMID 11751337.
  16. ^ Dimitrov D, He Y, Mutoh H, et al. (2007). "Engineering and characterization of an enhanced fluorescent protein voltage sensor". PLoS One. 2 (5): e440. Bibcode:2007PLoSO...2..440D. doi:10.1371/journal.pone.0000440. PMC 1857823. PMID 17487283.
  17. ^ Baker BJ, Lee H, Pieribone VA, et al. (2007). "Three fluorescent protein voltage sensors exhibit low plasma membrane expression in mammalian cells". J. Neurosci. Methods. 161 (1): 32–38. doi:10.1016/j.jneumeth.2006.10.005. PMID 17126911. S2CID 8540453.
  18. ^ Lundby A, Mutoh H, Dimitrov D, et al. (2008). "Engineering of a genetically encodable fluorescent voltage sensor exploiting fast Ci-VSP voltage-sensing movements". PLoS One. 3 (6): e2514. Bibcode:2008PLoSO...3.2514L. doi:10.1371/journal.pone.0002514. PMC 2429971. PMID 18575613.
  19. ^ Tsutsui H, Karasawa S, Okamura Y, et al. (2008). "Improving membrane voltage measurements using FRET with new fluorescent proteins". Nat. Methods. 5 (8): 683–685. doi:10.1038/nmeth.1235. PMID 18622396. S2CID 30661869.
  20. ^ Sjulson L, Miesenböck G (2008). "Rational optimization and imaging in vivo of a genetically encoded optical voltage reporter". J. Neurosci. 28 (21): 5582–5593. doi:10.1523/JNEUROSCI.0055-08.2008. PMC 2714581. PMID 18495892.
  21. ^ Perron A, Mutoh H, Launey T, et al. (2009). "Red-shifted voltage-sensitive fluorescent proteins". Chem. Biol. 16 (12): 1268–1277. doi:10.1016/j.chembiol.2009.11.014. PMC 2818747. PMID 20064437.
  22. ^ a b Kralj JM, Hochbaum DR, Douglass AD, et al. (2011). "Electrical spiking in Escherichia coli probed with a fluorescent voltage-indicating protein". Science. 333 (6040): 345–348. Bibcode:2011Sci...333..345K. doi:10.1126/science.1204763. PMID 21764748. S2CID 2195943.
  23. ^ Baker BJ, Jin L, Han Z, et al. (2012). "Genetically encoded fluorescent voltage sensors using the voltage-sensing domain of Nematostella and Danio phosphatases exhibit fast kinetics". J. Neurosci. Methods. 208 (2): 190–196. doi:10.1016/j.jneumeth.2012.05.016. PMC 3398169. PMID 22634212.
  24. ^ Jin L, Han Z, Platisa J, et al. (2012). "Single action potentials and subthreshold electrical events imaged in neurons with a fluorescent protein voltage probe". Neuron. 75 (5): 779–785. doi:10.1016/j.neuron.2012.06.040. PMC 3439164. PMID 22958819.
  25. ^ Kralj JM, Douglass AD, Hochbaum DR, et al. (2011). "Optical recording of action potentials in mammalian neurons using a microbial rhodopsin". Nat. Methods. 9 (1): 90–95. doi:10.1038/nmeth.1782. PMC 3248630. PMID 22120467.
  26. ^ Barnett L, Platisa J, Popovic M, et al. (2012). "A fluorescent, genetically-encoded voltage probe capable of resolving action potentials". PLoS One. 7 (9): e43454. Bibcode:2012PLoSO...743454B. doi:10.1371/journal.pone.0043454. PMC 3435330. PMID 22970127.
  27. ^ Akemann W, Mutoh H, Perron A, et al. (2012). "Imaging neural circuit dynamics with a voltage-sensitive fluorescent protein". J. Neurophysiol. 108 (8): 2323–2337. doi:10.1152/jn.00452.2012. PMID 22815406.
  28. ^ Lam AJ, St-Pierre F, Gong Y, et al. (2013). "Improving FRET Dynamic Range with Bright Green and Red Fluorescent Proteins". Biophys. J. 104 (2): 1005–1012. Bibcode:2013BpJ...104..683L. doi:10.1016/j.bpj.2012.11.3773. PMC 3461113. PMID 22961245.
  29. ^ Tsutsui H, Jinno Y, Tomita A, et al. (2013). "Improved detection of electrical activity with a voltage probe based on a voltage-sensing phosphatase". J. Physiol. (Lond.). 591 (18): 4427–4437. doi:10.1113/jphysiol.2013.257048. PMC 3784191. PMID 23836686.
  30. ^ Gong Y, Wagner MJ, Zhong Li J, et al. (2014). "Imaging neural spiking in brain tissue using FRET-opsin protein voltage sensors". Nat. Commun. 5: 3674. Bibcode:2014NatCo...5.3674G. doi:10.1038/ncomms4674. PMC 4247277. PMID 24755708.
  31. ^ Hochbaum DR, Zhao Y, Farhi SL, et al. (2014). "All-optical electrophysiology in mammalian neurons using engineered microbial rhodopsins". Nat. Methods. 11 (8): 825–833. doi:10.1038/nmeth.3000. PMC 4117813. PMID 24952910.
  32. ^ Flytzanis NC, Bedbrook CN, Chiu H, et al. (2014). "Archaerhodopsin variants with enhanced voltage-sensitive fluorescence in mammalian and Caenorhabditis elegans neurons". Nat. Commun. 5: 4894. Bibcode:2014NatCo...5.4894F. doi:10.1038/ncomms5894. PMC 4166526. PMID 25222271.
  33. ^ a b Gong Y, Huang C, Li JZ, et al. (2015). "High-speed recording of neural spikes in awake mice and flies with a fluorescent voltage sensor". Science. 350 (6266): 1361–1366. Bibcode:2015Sci...350.1361G. doi:10.1126/science.aab0810. PMC 4904846. PMID 26586188.
  34. ^ Treger JS, Priest MF, Bezanilla F (2015). "Single-molecule fluorimetry and gating currents inspire an improved optical voltage indicator". eLife. 4: e10482. doi:10.7554/eLife.10482. PMC 4658195. PMID 26599732.
  35. ^ Kang BE, Baker BJ (2016). "Pado, a fluorescent protein with proton channel activity can optically monitor membrane potential, intracellular pH, and map gap junctions". Sci. Rep. 6: 23865. Bibcode:2016NatSR...623865K. doi:10.1038/srep23865. PMC 4878010. PMID 27040905.
  36. ^ Yang HH, St-Pierre F, Sun X, et al. (2016). "Subcellular Imaging of Voltage and Calcium Signals Reveals Neural Processing In Vivo". Cell. 166 (1): 245–257. doi:10.1016/j.cell.2016.05.031. PMC 5606228. PMID 27264607.
  37. ^ Abdelfattah AS, Farhi SL, Zhao Y, et al. (2016). "A Bright and Fast Red Fluorescent Protein Voltage Indicator That Reports Neuronal Activity in Organotypic Brain Slices". J. Neurosci. 36 (8): 2458–2472. doi:10.1523/JNEUROSCI.3484-15.2016. PMC 4764664. PMID 26911693.
  38. ^ Lee S, Geiller T, Jung A, et al. (2017). "Improving a genetically encoded voltage indicator by modifying the cytoplasmic charge composition". Sci. Rep. 7 (1): 8286. Bibcode:2017NatSR...7.8286L. doi:10.1038/s41598-017-08731-2. PMC 5557843. PMID 28811673.
  39. ^ Chamberland, S; Yang, HH; Pan, MM; Evans, SW; Guan, S; Chavarha, M; Yang, Y; Salesse, C; Wu, H; Wu, JC; Clandinin, TR; Toth, K; Lin, MZ; St-Pierre, F (27 July 2017). "Fast two-photon imaging of subcellular voltage dynamics in neuronal tissue with genetically encoded indicators". eLife. 6. doi:10.7554/eLife.25690. PMC 5584994. PMID 28749338.
  40. ^ Lee EE, Bezanilla F (2017). "Biophysical Characterization of Genetically Encoded Voltage Sensor ASAP1: Dynamic Range Improvement". Biophys. J. 113 (10): 2178–2181. Bibcode:2017BpJ...113.2178L. doi:10.1016/j.bpj.2017.10.018. PMC 5700382. PMID 29108650.
  41. ^ Adam Y, Kim JJ, Lou S, et al. (2019). "Voltage imaging and optogenetics reveal behaviour-dependent changes in hippocampal dynamics". Nature. 569 (7756): 413–417. Bibcode:2019Natur.569..413A. doi:10.1038/s41586-019-1166-7. PMC 6613938. PMID 31043747.
    "We fused paQuasAr3 with a trafficking motif from the soma-localized KV2.1 potassium channel, which led to largely soma-localized expression (Fig. 2a, b). We called this construct paQuasAr3-s."
    "We called QuasAr3(V59A) 'photoactivated QuasAr3' (paQuasAr3)."
    "QuasAr2(K171R)-TS-citrine-TS-TS-TS-ER2, which we call QuasAr3."    {{cite journal}}: CS1 maint: postscript (link)
  42. ^ a b Liu, Zhuohe; Lu, Xiaoyu; Villette, Vincent; Gou, Yueyang; Colbert, Kevin L.; Lai, Shujuan; Guan, Sihui; Land, Michelle A.; Lee, Jihwan; Assefa, Tensae; Zollinger, Daniel R.; Korympidou, Maria M.; Vlasits, Anna L.; Pang, Michelle M.; Su, Sharon (2022-08-18). "Sustained deep-tissue voltage recording using a fast indicator evolved for two-photon microscopy". Cell. 185 (18): 3408–3425.e29. doi:10.1016/j.cell.2022.07.013. ISSN 0092-8674. PMC 9563101. PMID 35985322.
  43. ^ Yang HH, St-Pierre F (2016). "Genetically Encoded Voltage Indicators: Opportunities and Challenges". J. Neurosci. 36 (39): 9977–9989. doi:10.1523/JNEUROSCI.1095-16.2016. PMC 5039263. PMID 27683896.
  44. ^ Kaschula R, Salecker I (2016). "Neuronal Computations Made Visible with Subcellular Resolution". Cell. 166 (1): 18–20. doi:10.1016/j.cell.2016.06.022. PMID 27368098.
  45. ^ Cao G, Platisa J, Pieribone VA, et al. (2013). "Genetically targeted optical electrophysiology in intact neural circuits". Cell. 154 (4): 904–913. doi:10.1016/j.cell.2013.07.027. PMC 3874294. PMID 23932121.
  46. ^ Knöpfel T, Gallero-Salas Y, Song C (2015). "Genetically encoded voltage indicators for large scale cortical imaging come of age". Curr. Opin. Chem. Biol. 27: 75–83. doi:10.1016/j.cbpa.2015.06.006. PMID 26115448.
  47. ^ Kaestner L, Tian Q, Kaiser E, et al. (2015). "Genetically Encoded Voltage Indicators in Circulation Research". Int. J. Mol. Sci. 16 (9): 21626–21642. doi:10.3390/ijms160921626. PMC 4613271. PMID 26370981.
  48. ^ Zhang, Joe Z.; Termglinchan, Vittavat; Shao, Ning-Yi; Itzhaki, Ilanit; Liu, Chun; Ma, Ning; Tian, Lei; Wang, Vicky Y.; Chang, Alex C. Y.; Guo, Hongchao; Kitani, Tomoya (2019-05-02). "A Human iPSC Double-Reporter System Enables Purification of Cardiac Lineage Subpopulations with Distinct Function and Drug Response Profiles". Cell Stem Cell. 24 (5): 802–811.e5. doi:10.1016/j.stem.2019.02.015. ISSN 1934-5909. PMC 6499654. PMID 30880024.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Genetically_encoded_voltage_indicator&oldid=1235301857"