Control of Ca2+ influx and calmodulin activation by SK-channels in dendritic spines (article)
Griffith, T; Tsaneva-Atanasova, K; Mellor, JR
Date: 27 May 2016
Journal
PLoS Computational Biology
Publisher
Public Library of Science
Publisher DOI
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 voltagegated
Ca2+ -channel (VGCC) activation is thought to determine both the amplitude and direction
of synaptic plasticity by differential activation of Ca2+ ...
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.
Mathematics and Statistics
Faculty of Environment, Science and Economy
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