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Genetically encoded voltage indicator

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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] and Ace2N-mNeon.[5]

History

Despite that the idea of optical measurement of neuronal activity was proposed in the late 1960s,[6] 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,[7] 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 seldomly 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.[8]

Structure

GEVI can have many configuration designs in order to realize voltage sensing function.[9] 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. Arch.

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.[10] 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[7] 1997 Shaker (K+ channel) GFP -
VSFP1[11] 2001 Rat Kv2.1 (K+ channel) FRET pair: CFP and YFP -
SPARC[12] 2002 Rat Na+ channel GFP -
VSFP2's[13] 2007 Ci-VSD FRET pair: CFP (Cerulean) and YFP (Citrine) VSFP1
Flare[14] 2007 Kv1.4 (K+ channel) YFP FlaSh
VSFP3.1[15] 2008 Ci-VSD CFP VSFP2's
Mermaid[16] 2008 Ci-VSD FRET pair: Marine GFP (mUKG) and OFP (mKOκ) VSFP2's
hVOS[17] 2008 Dipicrylamine GFP -
Red-shifted VSFP's[18] 2009 Ci-VSD RFP/YFP (Citrine, mOrange2, TagRFP, or mKate2) VSFP3.1
PROPS[19] 2011 Modified green-absorbing proteorhodopsin (GPR) Same as left -
Zahra, Zahra 2[20] 2012 Nv-VSD, Dr-VSD FRET pair: CFP (Cerulean) and YFP (Citrine) VSFP2's
ArcLight[21] 2012 Ci-VSD Modified super ecliptic pHluorin -
Arch[22] 2012 Archaerhodopsin 3 Same as left -
ElectricPk[23] 2012 Ci-VSD Circularly permuted EGFP VSFP3.1
VSFP-Butterfly[24] 2012 Ci-VSD FRET pair: YFP (mCitrine) and RFP (mKate2) VSFP2's
VSFP-CR[25] 2013 Ci-VSD FRET pair: GFP (Clover) and RFP(mRuby2) VSFP2.3
Mermaid2[26] 2013 Ci-VSD FRET pair: CFP (seCFP2) and YFP Mermaid
Mac GEVIs[27] 2014 Mac rhodopsin (FRET acceptor) FRET doner: mCitrine, or mOrange2 -
QuasAr1, QuasAr2[28] 2014 Modified Archaerhodopsin 3 Same as left Arch
Archer[29] 2014 Modified Archaerhodopsin 3 Same as left Arch
ASAP1[3] 2014 Modified Gg-VSD Circularly permuted GFP -
Ace GEVIs[30] 2015 Modified Ace rhodopsin FRET doner: mNeonGreen Mac GEVIs
ArcLightning[31] 2015 Ci-VSD Modified super ecliptic pHluorin ArcLight
Pado[32] 2016 Voltage-gated proton channel Super ecliptic pHluorin -
ASAP2f[33] 2016 Modified Gg-VSD Circularly permuted GFP ASAP1
FlicR1[34] 2016 Ci-VSD Circularly permuted RFP (mApple) VSFP3.1
Bongwoori[35] 2017 Ci-VSD Modified super ecliptic pHluorin ArcLight
ASAP2s[36] 2017 Modified Gg-VSD Circularly permuted GFP ASAP1
ASAP-Y[37] 2017 Modified Gg-VSD Circularly permuted GFP ASAP1
(pa)QuasAr3(-s)[38] 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
  1. ↑Names in italic denote GEVIs not named.

Characteristics

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.[39] 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

Different types of GEVIs are seen being used 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 can show neuron signals with subcellular spatial resolution.[40] It has fast temporal resolution (sub-millisecond[30]), matching or surpassing that of the electrode recordings, and about one magnitude faster than calcium imaging. Researchers have used it to probe neural communications of an intact brain (of Drosophila[41] or mouse[42]), electrical spiking of bacteria (E. coli[19]), and human stem-cell derived cardiomyocyte.[43]

References

  1. ^ "Genetically-Encoded Voltage Indicators". Openoptogenetics.org. Retrieved 8 May 2017.{{cite web}}: CS1 maint: url-status (link)
  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, 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. doi:10.1038/nn.3709. PMC 4494739. PMID 24755780. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  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. ^ 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. doi:10.1126/science.aab0810. PMC 4904846. PMID 26586188.
  6. ^ Cohen LB, Keynes RD, Hille B (1968). "Light scattering and birefringence changes during nerve activity". Nature. 218 (5140): 438–441. doi:10.1038/218438a0. PMID 5649693.
  7. ^ 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.
  8. ^ Platisa J, Vasan G, Yang A, Pieribone VA (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. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  9. ^ 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.
  10. ^ Murata Y, Iwasaki H, Sasaki M, Inaba K, Okamura Y (2005). "Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor". Nature. 435 (7046): 1239–1243. doi:10.1038/nature03650. PMID 15902207. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  11. ^ Sakai R, Repunte-Canonigo V, Raj CD, Knöpfel T (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. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  12. ^ Ataka K, Pieribone VA (2002). "A genetically targetable fluorescent probe of channel gating with rapid kinetics". Biophys. J. 82 (1 Pt 1): 509–516. doi:10.1016/S0006-3495(02)75415-5. PMC 1302490. PMID 11751337.
  13. ^ Dimitrov D, He Y, Mutoh H, Baker BJ, Cohen L, Akemann W, Knöpfel T (2007). "Engineering and characterization of an enhanced fluorescent protein voltage sensor". PLoS One. 2 (5): e440. doi:10.1371/journal.pone.0000440. PMC 1857823. PMID 17487283. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)CS1 maint: unflagged free DOI (link)
  14. ^ 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 (1): 32–38. doi:10.1016/j.jneumeth.2006.10.005. PMID 17126911. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  15. ^ 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 (6): e2514. doi:10.1371/journal.pone.0002514. PMC 2429971. PMID 18575613. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)CS1 maint: unflagged free DOI (link)
  16. ^ Tsutsui H, Karasawa S, Okamura Y, Miyawaki A (2008). "Improving membrane voltage measurements using FRET with new fluorescent proteins". Nat. Methods. 5 (8): 683–685. doi:10.1038/nmeth.1235. PMID 18622396. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  17. ^ 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.
  18. ^ Perron A, Mutoh H, Launey T, Knöpfel T (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. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  19. ^ a b Kralj JM, Hochbaum DR, Douglass AD, Cohen AE (2011). "Electrical spiking in Escherichia coli probed with a fluorescent voltage-indicating protein". Science. 333 (6040): 345–348. doi:10.1126/science.1204763. PMID 21764748. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  20. ^ Baker BJ, Jin L, Han Z, Cohen LB, Popovic M, Platisa J, Pieribone V (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. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  21. ^ Jin L, Han Z, Platisa J, Wooltorton JR, Cohen LB, Pieribone VA (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. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  22. ^ Kralj JM, Douglass AD, Hochbaum DR, Maclaurin D, Cohen AE (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. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  23. ^ Barnett L, Platisa J, Popovic M, Pieribone VA, Hughes T (2012). "A fluorescent, genetically-encoded voltage probe capable of resolving action potentials". PLoS One. 7 (9): e43454. doi:10.1371/journal.pone.0043454. PMC 3435330. PMID 22970127. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)CS1 maint: unflagged free DOI (link)
  24. ^ Akemann W, Mutoh H, Perron A, Park YK, Iwamoto Y, Knöpfel T (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. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  25. ^ Lam AJ, St-Pierre F, Gong Y, Marshall JD, Cranfill PJ, Baird MA, McKeown MR, Wiedenmann J, Davidson MW, Schnitzer MJ, Tsien RY, Lin MZ (2013). "Improving FRET Dynamic Range with Bright Green and Red Fluorescent Proteins". Biophys. J. 104 (2): 683a. doi:10.1016/j.bpj.2012.11.3773. PMC 3461113. PMID 22961245. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  26. ^ Tsutsui H, Jinno Y, Tomita A, Niino Y, Yamada Y, Mikoshiba K, Miyawaki A, Okamura Y (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. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  27. ^ 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. doi:10.1038/ncomms4674. PMC 4247277. PMID 24755708. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  28. ^ 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. doi:10.1038/nmeth.3000. PMC 4117813. PMID 24952910. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  29. ^ Flytzanis NC, Bedbrook CN, Chiu H, Engqvist MK, Xiao C, Chan KY, Sternberg PW, Arnold FH, Gradinaru V (2014). "Archaerhodopsin variants with enhanced voltage-sensitive fluorescence in mammalian and Caenorhabditis elegans neurons". Nat. Commun. 5: 4894. doi:10.1038/ncomms5894. PMC 4166526. PMID 25222271. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  30. ^ a b Gong Y, Huang C, Li JZ, Grewe BF, Zhang Y, Eismann S, Schnitzer MJ (2015). "High-speed recording of neural spikes in awake mice and flies with a fluorescent voltage sensor". Science. 350 (6266): 1361–1366. doi:10.1126/science.aab0810. PMC 4904846. PMID 26586188. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  31. ^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  32. ^ 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. doi:10.1038/srep23865. PMC 4878010. PMID 27040905.
  33. ^ Yang HH, St-Pierre F, Sun X, Ding X, Lin MZ, Clandinin TR (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. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  34. ^ Abdelfattah AS, Farhi SL, Zhao Y, Brinks D, Zou P, Ruangkittisakul A, Platisa J, Pieribone VA, Ballanyi K, Cohen AE, Campbell RE (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. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  35. ^ Lee S, Geiller T, Jung A, Nakajima R, Song YK, Baker BJ (2017). "Improving a genetically encoded voltage indicator by modifying the cytoplasmic charge composition". Sci. Rep. 7 (1): 8286. doi:10.1038/s41598-017-08731-2. PMC 5557843. PMID 28811673. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  36. ^ 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.
  37. ^ Lee EE, Bezanilla F (2017). "Biophysical Characterization of Genetically Encoded Voltage Sensor ASAP1: Dynamic Range Improvement". Biophys. J. 113 (10): 2178–2181. doi:10.1016/j.bpj.2017.10.018. PMC 5700382. PMID 29108650.
  38. ^ Adam Y, Kim JJ, Lou S, Zhao Y, Xie ME, Brinks D, Wu H, Mostajo-Radji MA, Kheifets S, Parot V, Chettih S, Williams KJ, Gmeiner B, Farhi SL, Madisen L, Buchanan EK, Kinsella I, Zhou D, Paninski L, Harvey CD, Zeng H, Arlotta P, Campbell RE, Cohen AE (2019). "Voltage imaging and optogenetics reveal behaviour-dependent changes in hippocampal dynamics". Nature. 569 (7756): 413–417. 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}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)CS1 maint: postscript (link)
  39. ^ 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.
  40. ^ 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.
  41. ^ Cao G, Platisa J, Pieribone VA, Raccuglia D, Kunst M, Nitabach MN (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. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  42. ^ 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.
  43. ^ Kaestner L, Tian Q, Kaiser E, Xian W, Müller A, Oberhofer M, Ruppenthal S, Sinnecker D, Tsutsui H, Miyawaki A, Moretti A, Lipp P (2015). "Genetically Encoded Voltage Indicators in Circulation Research". Int. J. Mol. Sci. 16 (9): 21626–21642. doi:10.3390/ijms160921626. PMC 4613271. PMID 26370981. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)CS1 maint: unflagged free DOI (link)
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