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Calcium Input Frequency, Duration and Amplitude Differentially Modulate the Relative Activation of Calcineurin and CaMKII

Li, Lu and Stefan, Melanie I. and Le Novère, Nicolas (2012) Calcium Input Frequency, Duration and Amplitude Differentially Modulate the Relative Activation of Calcineurin and CaMKII. PLoS ONE, 7 (9). e43810. ISSN 1932-6203. PMCID PMC3433481. doi:10.1371/journal.pone.0043810. https://resolver.caltech.edu/CaltechAUTHORS:20121108-110230259

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Abstract

NMDA receptor dependent long-term potentiation (LTP) and long-term depression (LTD) are two prominent forms of synaptic plasticity, both of which are triggered by post-synaptic calcium elevation. To understand how calcium selectively stimulates two opposing processes, we developed a detailed computational model and performed simulations with different calcium input frequencies, amplitudes, and durations. We show that with a total amount of calcium ions kept constant, high frequencies of calcium pulses stimulate calmodulin more efficiently. Calcium input activates both calcineurin and Ca2+/calmodulin-dependent protein kinase II (CaMKII) at all frequencies, but increased frequencies shift the relative activation from calcineurin to CaMKII. Irrespective of amplitude and duration of the inputs, the total amount of calcium ions injected adjusts the sensitivity of the system to calcium input frequencies. At a given frequency, the quantity of CaMKII activated is proportional to the total amount of calcium. Thus, an input of a small amount of calcium at high frequencies can induce the same activation of CaMKII as a larger amount, at lower frequencies. Finally, the extent of activation of CaMKII signals with high calcium frequency is further controlled by other factors, including the availability of calmodulin, and by the potency of phosphatase inhibitors.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1371/journal.pone.0043810 DOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc3433481/PubMed CentralArticle
ORCID:
AuthorORCID
Le Novère, Nicolas0000-0002-6309-7327
Additional Information:© 2012 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received March 4, 2012; Accepted July 26, 2012; Published September 4, 2012. Editor: Zhong-Ping Feng, University of Toronto, Canada. Funding: These authors have no support or funding to report. Competing Interests: The authors have declared that no competing interests exist. We thank Stuart J. Edelstein and Massimo Lai for helpful suggestions during the modelling work, and the E-Cell team for providing technical support. Author Contributions: Conceived and designed the experiments: LL MIS NL. Performed the experiments: LL. Analyzed the data: LL. Contributed reagents/materials/ analysis tools: LL MIS. Wrote the paper: LL MIS NL.
Issue or Number:9
PubMed Central ID:PMC3433481
DOI:10.1371/journal.pone.0043810
Record Number:CaltechAUTHORS:20121108-110230259
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20121108-110230259
Official Citation:Li L, Stefan MI, Le Nove`re N (2012) Calcium Input Frequency, Duration and Amplitude Differentially Modulate the Relative Activation of Calcineurin and CaMKII. PLoS ONE 7(9): e43810. doi:10.1371/journal.pone.0043810
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:35363
Collection:CaltechAUTHORS
Deposited By: Melanie Stefan
Deposited On:08 Nov 2012 19:18
Last Modified:09 Nov 2021 23:14

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