Genetically encoded voltage indicator

Last updated

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]

Contents

History

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

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] YearSensingReportingPrecursor
FlaSh [9] 1997Shaker (K+ channel)GFP-
VSFP1 [14] 2001Rat Kv2.1 (K+ channel) FRET pair: CFP and YFP-
SPARC [15] 2002Rat Na+ channelGFP-
VSFP2's [16] 2007Ci-VSD FRET pair: CFP (Cerulean) and YFP (Citrine)VSFP1
Flare [17] 2007Kv1.4 (K+ channel)YFPFlaSh
VSFP3.1 [18] 2008Ci-VSDCFPVSFP2's
Mermaid [19] 2008Ci-VSD FRET pair: Marine GFP (mUKG) and OFP (mKOκ)VSFP2's
hVOS [20] 2008 Dipicrylamine GFP-
Red-shifted VSFP's [21] 2009Ci-VSDRFP/YFP (Citrine, mOrange2, TagRFP, or mKate2)VSFP3.1
PROPS [22] 2011Modified green-absorbing proteorhodopsin (GPR)Same as left-
Zahra, Zahra 2 [23] 2012Nv-VSD, Dr-VSD FRET pair: CFP (Cerulean) and YFP (Citrine)VSFP2's
ArcLight [24] 2012Ci-VSDModified super ecliptic pHluorin-
Arch [25] 2012 Archaerhodopsin 3 Same as left-
ElectricPk [26] 2012Ci-VSDCircularly permuted EGFPVSFP3.1
VSFP-Butterfly [27] 2012Ci-VSD FRET pair: YFP (mCitrine) and RFP (mKate2)VSFP2's
VSFP-CR [28] 2013Ci-VSD FRET pair: GFP (Clover) and RFP(mRuby2)VSFP2.3
Mermaid2 [29] 2013Ci-VSD FRET pair: CFP (seCFP2) and YFPMermaid
Mac GEVIs [30] 2014Mac rhodopsin (FRET acceptor)FRET doner: mCitrine, or mOrange2-
QuasAr1, QuasAr2 [31] 2014Modified Archaerhodopsin 3Same as leftArch
Archer [32] 2014Modified Archaerhodopsin 3Same as leftArch
ASAP1 [3] 2014Modified Gg-VSDCircularly permuted GFP-
Ace GEVIs [33] 2015Modified Ace rhodopsinFRET doner: mNeonGreenMac GEVIs
ArcLightning [34] 2015Ci-VSDModified super ecliptic pHluorinArcLight
Pado [35] 2016Voltage-gated proton channelSuper ecliptic pHluorin-
ASAP2f [36] 2016Modified Gg-VSDCircularly permuted GFPASAP1
FlicR1 [37] 2016Ci-VSDCircularly permuted RFP (mApple)VSFP3.1
Bongwoori [38] 2017Ci-VSDModified super ecliptic pHluorin ArcLight
ASAP2s [39] 2017Modified Gg-VSDCircularly permuted GFPASAP1
ASAP-Y [40] 2017Modified Gg-VSDCircularly permuted GFPASAP1
(pa)QuasAr3(-s) [41] 2019Modified Archaerhodopsin 3Same as leftQuasAr2
Voltron(-ST)2019Modified Ace rhodopsin (Ace2)FRET doner: Janelia Fluor (chemical)-
ASAP3 [4] 2019Modified Gg-VSDCircularly permuted GFPASAP2s
JEDI-2P [42] 2022Modified Gg-VSDCircularly permuted GFPASAP2s
  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. [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

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

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, JEDI-2P, the latest generation of GEIV, is a fast, sensitive, bright, and photostable two-photon-compatible sensor which is considered to be almost perfect for many challenging deep-tissue imaging applications. [42] However, 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.

Related Research Articles

Channelrhodopsins are a subfamily of retinylidene proteins (rhodopsins) that function as light-gated ion channels. They serve as sensory photoreceptors in unicellular green algae, controlling phototaxis: movement in response to light. Expressed in cells of other organisms, they enable light to control electrical excitability, intracellular acidity, calcium influx, and other cellular processes. Channelrhodopsin-1 (ChR1) and Channelrhodopsin-2 (ChR2) from the model organism Chlamydomonas reinhardtii are the first discovered channelrhodopsins. Variants that are sensitive to different colors of light or selective for specific ions have been cloned from other species of algae and protists.

Cameleon is an engineered protein based on variant of green fluorescent protein used to visualize calcium levels in living cells. It is a genetically encoded calcium sensor created by Roger Y. Tsien and coworkers. The name is a conflation of CaM and chameleon to indicate the fact that the sensor protein undergoes a conformation change and radiates at an altered wavelength upon calcium binding to the calmodulin element of the Cameleon. Cameleon was the first genetically encoded calcium sensor that could be used for ratiometric measurements and the first to be used in a transgenic animal to record activity in neurons and muscle cells. Cameleon and other genetically encoded calcium indicators (GECIs) have found many applications in neuroscience and other fields of biology. It was created by fusing BFP, calmodulin, calmodulin-binding peptide M13 and EGFP.

<span class="mw-page-title-main">Hippocalcin</span> Protein-coding gene in the species Homo sapiens

Hippocalcin is a protein that in humans is encoded by the HPCA gene.

SCN2A Protein-coding gene in the species Homo sapiens

Sodium channel protein type 2 subunit alpha, is a protein that in humans is encoded by the SCN2A gene. Functional sodium channels contain an ion conductive alpha subunit and one or more regulatory beta subunits. Sodium channels which contain sodium channel protein type 2 subunit alpha are sometimes called Nav1.2 channels.

<span class="mw-page-title-main">Visinin-like protein 1</span> Protein-coding gene in the species Homo sapiens

Visinin-like protein 1 is a protein that in humans is encoded by the VSNL1 gene.

<span class="mw-page-title-main">NRCAM</span> Protein-coding gene in the species Homo sapiens

Neuronal cell adhesion molecule is a protein that in humans is encoded by the NRCAM gene.

<span class="mw-page-title-main">Hippocalcin-like protein 1</span> Protein-coding gene in the species Homo sapiens

Hippocalcin-like protein 1 is a protein that in humans is encoded by the HPCAL1 gene.

<span class="mw-page-title-main">KCNIP1</span> Protein-coding gene in the species Homo sapiens

Kv channel-interacting protein 1 also known as KChIP1 is a protein that in humans is encoded by the KCNIP1 gene.

<span class="mw-page-title-main">KCNIP4</span> Protein-coding gene in the species Homo sapiens

Kv channel-interacting protein 4 is a protein that in humans is encoded by the KCNIP4 gene.

<span class="mw-page-title-main">Axon terminal</span> Nerve fiber part

Axon terminals are distal terminations of the branches of an axon. An axon, also called a nerve fiber, is a long, slender projection of a nerve cell that conducts electrical impulses called action potentials away from the neuron's cell body in order to transmit those impulses to other neurons, muscle cells or glands. In the central nervous system, most presynaptic terminals are actually formed along the axons, not at their ends.

<span class="mw-page-title-main">RoGFP</span> Prodified GFP protein that exhibits different fluorescent properties when oxidized and reduced

The reduction-oxidation sensitive green fluorescent protein (roGFP) is a green fluorescent protein engineered to be sensitive to changes in the local redox environment. roGFPs are used as redox-sensitive biosensors.

Fluorescent chloride sensors are used for chemical analysis. The discoveries of chloride (Cl−) participations in physiological processes stimulates the measurements of intracellular Cl− in live cells and the development of fluorescent tools referred below.

<span class="mw-page-title-main">GCaMP</span> Genetically encoded calcium indicator

GCaMP is a genetically encoded calcium indicator (GECI) initially developed in 2001 by Junichi Nakai. It is a synthetic fusion of green fluorescent protein (GFP), calmodulin (CaM), and M13, a peptide sequence from myosin light-chain kinase. When bound to Ca2+, GCaMP fluoresces green with a peak excitation wavelength of 480 nm and a peak emission wavelength of 510 nm. It is used in biological research to measure intracellular Ca2+ levels both in vitro and in vivo using virally transfected or transgenic cell and animal lines. The genetic sequence encoding GCaMP can be inserted under the control of promoters exclusive to certain cell types, allowing for cell-type specific expression of GCaMP. Since Ca2+ is a second messenger that contributes to many cellular mechanisms and signaling pathways, GCaMP allows researchers to quantify the activity of Ca2+-based mechanisms and study the role of Ca2+ ions in biological processes of interest.

<span class="mw-page-title-main">HVCN1</span> Protein-coding gene in the species Homo sapiens

Voltage-gated hydrogen channel 1 is a protein that in humans is encoded by the HVCN1 gene.

Calcium imaging is a microscopy technique to optically measure the calcium (Ca2+) status of an isolated cell, tissue or medium. Calcium imaging takes advantage of calcium indicators, fluorescent molecules that respond to the binding of Ca2+ ions by fluorescence properties. Two main classes of calcium indicators exist: chemical indicators and genetically encoded calcium indicators (GECI). This technique has allowed studies of calcium signalling in a wide variety of cell types. In neurons, action potential generation is always accompanied by rapid influx of Ca2+ ions. Thus, calcium imaging can be used to monitor the electrical activity in hundreds of neurons in cell culture or in living animals, which has made it possible observe the activity of neuronal circuits during ongoing behavior.

ArcLight is a genetically-encoded voltage indicator (GEVI) created from Ciona intestinalis voltage sensor and the fluorescent protein super ecliptic pHluorin that carries a critical point mutation (A227D).

<span class="mw-page-title-main">Archaerhodopsin</span> Family of archaea

Archaerhodopsin proteins are a family of retinal-containing photoreceptors found in the archaea genera Halobacterium and Halorubrum. Like the homologous bacteriorhodopsin (bR) protein, archaerhodopsins harvest energy from sunlight to pump H+ ions out of the cell, establishing a proton motive force that is used for ATP synthesis. They have some structural similarities to the mammalian GPCR protein rhodopsin, but are not true homologs.

A genetically engineered fluorescent protein that changes its fluorescence when bound to the neurotransmitter glutamate. Glutamate-sensitive fluorescent reporters are used to monitor the activity of presynaptic terminals by fluorescence microscopy. GluSnFRs are a class of optogenetic sensors used in neuroscience research. In brain tissue, two-photon microscopy is typically used to monitor GluSnFR fluorescence.

Michael Z. Lin is a Taiwanese-American biochemist and bioengineer. He is an Associate Professor of Neurobiology and Bioengineering at Stanford University. He is best known for his work on engineering optically and chemically controllable proteins.

Optogenetics began with methods to alter neuronal activity with light, using e.g. channelrhodopsins. In a broader sense, optogenetic approaches also include the use of genetically encoded biosensors to monitor the activity of neurons or other cell types by measuring fluorescence or bioluminescence. Genetically encoded calcium indicators (GECIs) are used frequently to monitor neuronal activity, but other cellular parameters such as membrane voltage or second messenger activity can also be recorded optically. The use of optogenetic sensors is not restricted to neuroscience, but plays increasingly important roles in immunology, cardiology and cancer research.

References

  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. 1 2 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. 1 2 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. 1 2 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. 1 2 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. 1 2 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. 1 2 3 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.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.