The Life Cycle of Ca2+ Ions in Dendritic Spines
Open accessAbstract
Spine Ca(2+) is critical for the induction of synaptic plasticity, but the factors that control Ca(2+) handling in dendritic spines under physiological conditions are largely unknown. We studied [Ca(2+)] signaling in dendritic spines of CA1 pyramidal neurons and find that spines are specialized structures with low endogenous Ca(2+) buffer capacity that allows large and extremely rapid [Ca(2+)] changes. Under physiological conditions, Ca(2+) diffusion across the spine neck is negligible, and the spine head functions as a separate compartment on long time scales, allowing localized Ca(2+) buildup during trains of synaptic stimuli. Furthermore, the kinetics of Ca(2+) sources governs the time course of [Ca(2+)] signals and may explain the selective activation of long-term synaptic potentiation (LTP) and long-term depression (LTD) by NMDA-R-mediated synaptic Ca(2+).
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The driving force for calcium entry is very large for a neuron at rest and the block of NMDARs by Mg2+ is incomplete even at resting potentials, so significant Ca enters the cell in response to synaptic stimulation during low-frequency synaptic stimulation.
“Because the driving force for calcium entry is very large for a neuron at rest and the block of NMDARs by Mg 2þ is incomplete even at resting potentials (Jahr and Stevens 1993), significant Ca enters the cell in response to synaptic stimulation (Sabatini et al. 2002;Bloodgood and Sabatini 2007;Bloodgood et al. 2009) during low-frequency synaptic stimulation.”
From NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD). (2012) · cites this paper as Sabatini et al. 2002
When calcium is bound to buffering proteins like calmodulin, the diffusion of the resulting complex is more sensitive to spatial constraints than single ions because of its larger size.
“Importantly, when calcium is bound to buffering proteins like calmodulin, the diffusion of the resulting complex is more sensitive to spatial constraints than single ions because of its larger size (Sabatini et al., 2002; Tønnesen et al., 2014).”
From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Sabatini et al., 2002
Long and thin necks prevent the diffusion of calcium, whereas shorter and thicker necks allow for better diffusional coupling with the dendrite.
“Nevertheless, morphology does play a role, as long and thin necks prevent the diffusion of calcium, whereas shorter and thicker necks allow for better diffusional coupling with the dendrite (Majewska et al., 2000; Holthoff et al., 2002; Sabatini et al., 2002; Korkotian et al., 2004; Noguchi et al., 2005).”
From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Sabatini et al., 2002
Calcium can also be removed from spines by absorption into the smooth endoplasmic reticulum located in spines or by Na/Ca exchangers located in the plasma membrane.
“In addition to diffusion into the dendritic shaft, calcium can also be removed from spines by absorption into the smooth endoplasmic reticulum located in spines or by Na/Ca exchangers located in the plasma membrane (Sabatini et al., 2002).”
From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Sabatini et al., 2002
If calcium-permeable ion channels were distributed equally throughout the plasma membrane, one would expect a higher effective concentration of these channels in spines compared to dendrites as the surface-to-volume ratio of the former is higher. This should theoretically lead to a higher influx of calcium in spines than in the surrounding dendrite.
“If these ion channels were distributed equally throughout the plasma membrane, one would expect a higher effective concentration of these channels in spines compared to dendrites as the surface-to-volume ratio of the former is higher. This should theoretically lead to a higher influx of calcium in spines than in the surrounding dendrite (Sabatini et al., 2002).”
From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Sabatini et al., 2002
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- Authors
- Sabatini, B. L., Oertner, T. G., & Svoboda, K.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Svoboda, Karel
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2002-01
- Volume
- 33
- Issue
- 3
- Pages
- 439-452
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2022286642
- Cited by
- 745
- References
- 5
- Citations by year
- 2026: 20 · 2025: 20 · 2024: 22 · 2023: 16 · 2022: 21 · 2021: 17 · 2020: 30 · 2019: 30 · 2018: 35 · 2017: 26 · 2016: 30 · 2015: 35 · 2014: 39 · 2013: 32 · 2012: 37
- FWCI
- 13.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- dendritic spines, calcium signaling, calcium buffering, calcium diffusion, synaptic plasticity, long-term potentiation, long-term depression, NMDA receptor, CA1 pyramidal neurons
- MeSH terms
- Action Potentials, Animals, Bicuculline, Buffers, Calcium, Cells, Cultured, Dendrites, Fluorescent Dyes, Hippocampus, Mathematics, Models, Neurological, Neurons, Quinoxalines, Receptors, N-Methyl-D-Aspartate, Microscopy, Confocal, Excitatory Amino Acid Antagonists, GABA Antagonists, Rats, In Vitro Techniques
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