Calcium input frequency, duration and amplitude differentially modulate the relative activation of calcineurin and CaMKII.

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 computa...

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Autores principales:	Lu Li, Melanie I Stefan, Nicolas Le Novère
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b94ee3fd9f65432d89bc6892ce023c70
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spelling	oai:doaj.org-article:b94ee3fd9f65432d89bc6892ce023c702021-11-18T07:06:45ZCalcium input frequency, duration and amplitude differentially modulate the relative activation of calcineurin and CaMKII.1932-620310.1371/journal.pone.0043810https://doaj.org/article/b94ee3fd9f65432d89bc6892ce023c702012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22962589/?tool=EBIhttps://doaj.org/toc/1932-6203NMDA 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 Ca(2+)/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.Lu LiMelanie I StefanNicolas Le NovèrePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e43810 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lu Li Melanie I Stefan Nicolas Le Novère Calcium input frequency, duration and amplitude differentially modulate the relative activation of calcineurin and CaMKII.
description	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 Ca(2+)/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.
format	article
author	Lu Li Melanie I Stefan Nicolas Le Novère
author_facet	Lu Li Melanie I Stefan Nicolas Le Novère
author_sort	Lu Li
title	Calcium input frequency, duration and amplitude differentially modulate the relative activation of calcineurin and CaMKII.
title_short	Calcium input frequency, duration and amplitude differentially modulate the relative activation of calcineurin and CaMKII.
title_full	Calcium input frequency, duration and amplitude differentially modulate the relative activation of calcineurin and CaMKII.
title_fullStr	Calcium input frequency, duration and amplitude differentially modulate the relative activation of calcineurin and CaMKII.
title_full_unstemmed	Calcium input frequency, duration and amplitude differentially modulate the relative activation of calcineurin and CaMKII.
title_sort	calcium input frequency, duration and amplitude differentially modulate the relative activation of calcineurin and camkii.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/b94ee3fd9f65432d89bc6892ce023c70
work_keys_str_mv	AT luli calciuminputfrequencydurationandamplitudedifferentiallymodulatetherelativeactivationofcalcineurinandcamkii AT melanieistefan calciuminputfrequencydurationandamplitudedifferentiallymodulatetherelativeactivationofcalcineurinandcamkii AT nicolaslenovere calciuminputfrequencydurationandamplitudedifferentiallymodulatetherelativeactivationofcalcineurinandcamkii
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Calcium input frequency, duration and amplitude differentially modulate the relative activation of calcineurin and CaMKII.

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