Control of Ca2+ influx and calmodulin activation by SK-channels in dendritic spines (article)
PLoS Computational Biology
Public Library of Science
This is the final version of the article. Available from PLoS via the DOI in this record.
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 voltagegated 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.
TG was supported by Engineering and Physical Sciences Research Council (EPSRC) grant EP/I013717/1. KTA was supported by grants EP/ L000296/1 and EP/N014391/1 of EPSRC. JRM was supported by Biotechnology and Biological Sciences Research Council and Wellcome Trust.
Dataset available at: http://hdl.handle.net/10871/21394
PLoS Computational Biology, 2016, Vol. 12(5): e1004949