Fast GCaMPs for improved tracking of neuronal activity

Xiaonan R. Sun, Aleksandra Badura, Diego A. Pacheco, Laura A. Lynch, Eve R. Schneider, Matthew P. Taylor, Ian B. Hogue, Lynn W. Enquist, Mala Murthy, Samuel S.H. Wang

Research output: Contribution to journalArticlepeer-review

109 Scopus citations


The use of genetically encodable calcium indicator proteins to monitor neuronal activity is hampered by slow response times and a narrow Ca2+-sensitive range. Here we identify three performance-limiting features of GCaMP3, a popular genetically encodable calcium indicator protein. First, we find that affinity is regulated by the calmodulin domain's Ca2+-chelating residues. Second, we find that off-responses to Ca2+ are rate-limited by dissociation of the RS20 domain from calmodulin's hydrophobic pocket. Third, we find that on-responses are limited by fast binding to the N-lobe at high Ca2+ and by slow binding to the C-lobe at lower Ca2+. We develop Fast-GCaMPs, which have up to 20-fold accelerated off-responses and show that they have a 200-fold range of KD, allowing coexpression of multiple variants to span an expanded range of Ca2+ concentrations. Finally, we show that Fast-GCaMPs track natural song in Drosophila auditory neurons and generate rapid responses in mammalian neurons, supporting the utility of our approach.

Original languageEnglish
Article number2170
JournalNature Communications
StatePublished - Jul 18 2013

Bibliographical note

Publisher Copyright:
© 2013 Macmillan Publishers Limited. All rights reserved.

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


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