Evidence map›Paper›PMID 25568129›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015

Combinatorial mutagenesis of the voltage-sensing domain enables the optical resolution of action potentials firing at 60 Hz by a genetically encoded fluorescent sensor of membrane potential.

Hong Hua Piao, Dhanarajan Rajakumar, Bok Eum Kang, Eun Ha Kim, Bradley J Baker

Abstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

53 citing papers in PubMed.

  1. Article
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  4. Harnessing Intelligence from Brain Cells In Vitro.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2025
    Review
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  7. Article
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  15. Article
  16. Imaging Voltage with Microbial Rhodopsins.Frontiers in molecular biosciences · 2021
    Review
  17. Review
  18. Review
  19. Article
  20. Genetic voltage indicators.BMC biology · 2019
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Hong Hua PiaoCenter for Functional Connectomics, Korea Institute of Science and Technology, Seongbuk-gu, Seoul, 136-791, Republic of Korea.
Dhanarajan RajakumarCenter for Functional Connectomics, Korea Institute of Science and Technology, Seongbuk-gu, Seoul, 136-791, Republic of Korea.
Bok Eum KangCenter for Functional Connectomics, Korea Institute of Science and Technology, Seongbuk-gu, Seoul, 136-791, Republic of Korea.
Eun Ha KimCenter for Functional Connectomics, Korea Institute of Science and Technology, Seongbuk-gu, Seoul, 136-791, Republic of Korea.
Bradley J BakerCenter for Functional Connectomics, Korea Institute of Science and Technology, Seongbuk-gu, Seoul, 136-791, Republic of Korea bradley.baker19@gmail.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

ArcLight is a genetically encoded fluorescent voltage sensor using the voltage-sensing domain of the voltage-sensing phosphatase from Ciona intestinalis that gives a large but slow-responding optical signal in response to changes in membrane potential (Jin et al., 2012). Fluorescent voltage sensors using the voltage-sensing domain from other species give faster yet weaker optical signals (Baker et al., 2012; Han et al., 2013). Sequence alignment of voltage-sensing phosphatases from different species revealed conserved polar and charged residues at 7 aa intervals in the S1-S3 transmembrane segments of the voltage-sensing domain, suggesting potential coil-coil interactions. The contribution of these residues to the voltage-induced optical signal was tested using a cassette mutagenesis screen by flanking each transmembrane segment with unique restriction sites to allow for the testing of individual mutations in each transmembrane segment, as well as combinations in all four transmembrane segments. Addition of a counter charge in S2 improved the kinetics of the optical response. A double mutation in the S4 domain dramatically reduced the slow component of the optical signal seen in ArcLight. Combining that double S4 mutant with the mutation in the S2 domain yielded a probe with kinetics <10 ms. Optimization of the linker sequence between S4 and the fluorescent protein resulted in a new ArcLight-derived probe, Bongwoori, capable of resolving action potentials in a hippocampal neuron firing at 60 Hz. Additional manipulation of the voltage-sensing domain could potentially lead to fluorescent sensors capable of optically resolving neuronal inhibition and subthreshold synaptic activity.

Indexed as

Sequence HomologyAction PotentialsAmino Acid SequenceAnimalsCiona intestinalisFluorescent DyesHEK293 CellsHumansIon Channel GatingIon ChannelsLuminescent ProteinsMembrane PotentialsMice, Inbred C57BLMolecular Sequence DataMutagenesisOptogeneticsFluorescent DyesIon ChannelsLuminescent Proteinsfluorescent proteinomega currentvoltage imagingvoltage-sensing domainvoltage-sensing phosphatasevoltage sensor

Identifiers

PMID25568129
PMCPMC6605254

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.