Journal article

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

  • Schwaller, Beat Unit of Anatomy, Department of Medicine, University of Fribourg, Switzerland
Published in:
  • Biochimica et Biophysica Acta (BBA) - General Subjects. - 2012, vol. 1820, no. 8, p. 1294-1303
English 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 SignificanceThe 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.
Faculté des sciences et de médecine
Département de Médecine
  • English
Biological sciences
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