Mechanisms of calcium decay kinetics in hippocampal spines: role of spine calcium pumps and calcium diffusion through the spine neck in biochemical compartmentalization
Open accessAbstract
Dendritic spines receive most excitatory inputs in the CNS and compartmentalize calcium. Although the mechanisms of calcium influx into spines have been explored, it is unknown what determines the calcium decay kinetics in spines. With two-photon microscopy we investigate action potential-induced calcium dynamics in spines from rat CA1 pyramidal neurons in slices. The [Ca 2+ ] i in most spines shows two decay kinetics: an initial fast component, during which [Ca 2+ ] i in spines decays to dendritic levels, followed by a slower decay phase in which the spine follows dendritic kinetics. The correlation between [Ca 2+ ] i in spine and dendrite at the breakpoint of the decay kinetics demonstrates diffusional equilibration between spine and dendrite during the slower component. To explain the faster initial decay, we rule out saturation or kinetic effects of endogenous or exogenous buffers and focus instead on (1) active calcium extrusion and (2) buffered diffusion of calcium from spine to dendrite. The presence of an undershoot in most spines indicates that extrusion mechanisms can be intrinsic to the spine. Supporting the two mechanisms, pharmacological blockade of smooth endoplasmic reticulum calcium (SERCA) pumps and the length of the spine neck affect spine decay kinetics. Using a mathematical model, we find that the contribution of calcium pumps and diffusion varies from spine to spine. We conclude that dendritic spines have calcium pumps and that their density and kinetics, together with the morphology of the spine neck, determine the time during which the spine compartmentalizes calcium.
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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 Majewska et al., 2000
In “Functional regulation of calcium pumps and spine neck length” (page unavailable), the paper says diffusion between spine and dendrite depends on neck length, supporting the contrast between longer and shorter necks. It does not establish that long, thin necks prevent calcium diffusion or directly show that thicker necks improve coupling. The “Buffered calcium diffusion across the spine neck” section describes diffusion between the compartments, so “prevent” overstates the finding. (LLM, conf=0.88)
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References 50 · Cited by 248
Research works printed but not linked: 3
- Bevington PR, Robinson DK (1992) Data reduction and error analysis for the physical sciences. Boston: WCB/McGraw-Hill.
- Guerini D, Carafoli E (1999) The calcium pumps. In: Calcium as a cellular regulator (Carafoli E, Klee C, eds), pp 249 -278. New York: Oxford UP.
- Philipson K D (1999) Sodium -calcium exchange. In: C alcium as a cellular regulator (C arafoli E, K lee C, eds), pp 279 -294. New York: Oxford UP.
- Authors
- Majewska, A., Brown, E., Ross, J., & Yuste, R.
- Affiliations
- Columbia University (US)
- Cornell University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2000-03-01
- Volume
- 20
- Issue
- 5
- Pages
- 1722-1734
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6772925
- OpenAlex
- W1577778731
- Cited by
- 248
- References
- 50
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 6 · 2022: 6 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 6 · 2015: 7 · 2014: 10 · 2013: 12 · 2012: 13
- FWCI
- 6.47
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- March of Dimes Foundation
- Arnold and Mabel Beckman Foundation
- National Eye Institute (EY111787)
- 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 › Neural dynamics and brain function
- Keywords
- dendritic spines, calcium pump, sarcoplasmic reticulum Ca2+-ATPase, calcium diffusion, calcium compartmentalization, CA1 pyramidal neurons, calcium buffering, calcium efflux, mathematical modeling
- MeSH terms
- Action Potentials, Animals, Biological Transport, Buffers, Calcium, Cell Compartmentation, Dendrites, Diffusion, Hippocampus, Kinetics, Models, Chemical, Synaptic Transmission, Calcium Channels, Linear Models, Rats, Sprague-Dawley, Nonlinear Dynamics, Pyramidal Cells, Rats, In Vitro Techniques
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