Control of Ca2+ influx and calmodulin activation by SK-channels in dendritic spines

Blackwell, Kim T., Griffith, Thom, Tsaneva-Atanasova, Krasimira and Mellor, Jack R. 2016. Control of Ca2+ influx and calmodulin activation by SK-channels in dendritic spines. PLoS Computational Biology 12 (5) , e1004949. 10.1371/journal.pcbi.1004949

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Abstract

The key trigger for Hebbian synaptic plasticity is influx of Ca2+ into postsynaptic dendritic spines. The magnitude of [Ca2+] increase caused by NMDA-receptor (NMDAR) and voltage-gated Ca2+ -channel (VGCC) activation is thought to determine both the amplitude and direction of synaptic plasticity by differential activation of Ca2+ -sensitive enzymes such as calmodulin. Ca2+ influx is negatively regulated by Ca2+ -activated K+ channels (SK-channels) which are in turn inhibited by neuromodulators such as acetylcholine. However, the precise mechanisms by which SK-channels control the induction of synaptic plasticity remain unclear. Using a 3-dimensional model of Ca2+ and calmodulin dynamics within an idealised, but biophysically-plausible, dendritic spine, we show that SK-channels regulate calmodulin activation specifically during neuron-firing patterns associated with induction of spike timing-dependent plasticity. SK-channel activation and the subsequent reduction in Ca2+ influx through NMDARs and L-type VGCCs results in an order of magnitude decrease in calmodulin (CaM) activation, providing a mechanism for the effective gating of synaptic plasticity induction. This provides a common mechanism for the regulation of synaptic plasticity by neuromodulators.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Schools > Psychology
Publisher:	Public Library of Science
ISSN:	1553-7358
Date of First Compliant Deposit:	2 September 2025
Date of Acceptance:	16 April 2016
Last Modified:	02 Sep 2025 09:00
URI:	https://orca.cardiff.ac.uk/id/eprint/180765

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