Control of Ca2+ Influx and Calmodulin Activation by SK-Channels in Dendritic Spines

Mellor, Jack R.; Griffith, Thom; Tsaneva-Atanasova, Krasimira; Mellor, Jack

Abstract

© 2016 Griffith et al. 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.

Citation

Mellor, J. R., Griffith, T., Tsaneva-Atanasova, K., & Mellor, J. (2016). Control of Ca2+ Influx and Calmodulin Activation by SK-Channels in Dendritic Spines. PLoS Computational Biology, 12(5), e1004949. https://doi.org/10.1371/journal.pcbi.1004949

• Journal Article Type: Article
• Acceptance Date: May 10, 2016
• Publication Date: May 1, 2016
• Deposit Date: Apr 27, 2017
• Publicly Available Date: Apr 27, 2017
• Journal: PLoS Computational Biology
• Print ISSN: 1553-734X
• Electronic ISSN: 1553-7358
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Issue: 5
• Pages: e1004949
• DOI: https://doi.org/10.1371/journal.pcbi.1004949
• Keywords: control, Ca2+ influx, calmodulin activation, SK-channels, dendric spines
• Public URL: https://uwe-repository.worktribe.com/output/1433955
• Publisher URL: http://dx.doi.org/10.1371/journal.pcbi.1004949