Cited by 75Ion channel regulation and functionIon Channels and ReceptorsNeuroscience and Neuropharmacology Research

The use of transgenic mouse models to reveal the functions of Ca2+ buffer proteins in excitable cells

Schwaller, Beat·2012·Biochimica et Biophysica Acta (BBA) - General Subjects

Abstract

Background Cytosolic Ca2+ buffers are members of the large family of Ca2+-binding proteins and are essential components of the Ca2+ signaling toolkit implicated in the precise regulation of intracellular Ca2+ signals. Their physiological role in excitable cells has been investigated in vivo by analyzing the phenotype of mice either lacking one of the Ca2+ buffers or mice with ectopic expression.Scope of review In this review, results obtained with knockout mice for the three most prominent Ca2+ buffers, parvalbumin, calbindin-D28k and calretinin are summarized.Major conclusions The absence of Ca2+ buffers in specific neuron subpopulations, and for parvalbumin additionally in fast-twitch muscles, leads to Ca2+ buffer-specific changes in intracellular Ca2+ signals. This affects the excitation-contraction cycle in parvalbumin-deficient muscles, and in Ca2+ buffer-deficient neurons, properties associated with synaptic transmission (e.g. short-term modulation), excitability and network oscillations are altered. These findings have not only resulted in a better understanding of the physiological function of Ca2+ buffers, but have revealed that the absence of Ca2+ signaling toolkit components leads to protein-and neuron-specific adaptive/homeostatic changes that also include changes in neuron morphology (e.g. altered spine morphology, changes in mitochondria content) and network properties.General significance The complex phenotype of Ca2+ buffer knockout mice arises from the direct effect of these proteins on Ca2+ signaling and moreover from the homeostatic mechanisms induced in these mice. For a better mechanistic understanding of neurological diseases linked to disturbed/altered Ca2+ signaling, a global view on Ca2+ signaling is expected to lead to new avenues for specific therapies. This article is part of a Special Issue entitled Biochemical, biophysical and genetic approaches to intracellular calcium signaling.

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Crossref · 10.1016/j.bbagen.2011.11.008

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Authors
Schwaller, B.
Affiliations
University of Fribourg (CH)
Corresponding author
Schwaller, Beat
Venue
Biochimica et Biophysica Acta (BBA) - General Subjects
Publisher
Elsevier BV
Published
2012-08
Volume
1820
Issue
8
Pages
1294-1303
ISSN
0304-4165 (ISSN-L)
OpenAlex
W2144096695
Cited by
75
References
110
Citations by year
2026: 2 · 2024: 2 · 2023: 5 · 2022: 5 · 2021: 7 · 2020: 5 · 2019: 2 · 2018: 8 · 2017: 4 · 2016: 9 · 2015: 7 · 2014: 8 · 2013: 6 · 2012: 4
FWCI
0.52
Type
journal article
Language
en
Open access
closed
Locations
  • Biochimica et Biophysica Acta (BBA) - General Subjects (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
parvalbumin, calbindin-D28k, calretinin, calcium signaling, excitable cells, knockout mice, excitation-contraction coupling, fast-twitch muscle, synaptic transmission, neuronal excitability, network oscillations, homeostatic adaptation, dendritic spine morphology, mitochondrial content, neurological disorders
MeSH terms
Animals, Humans, Mice, Transgenic, Mitochondria, Muscle, Neurons, Parvalbumins, Phenotype, Calcium Signaling, Mice, Calbindins, S100 Calcium Binding Protein G, Calbindin 2, Calbindin 1

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