title: The use of transgenic mouse models to reveal the functions of Ca2+ buffer proteins in excitable cells.
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.
  
  
  METHODS
  In this review, results obtained with knockout mice for the three most prominent Ca2+ buffers, parvalbumin, calbindin-D28k and calretinin are summarized.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Unit of Anatomy, Department of Medicine, University of Fribourg, Fribourg, Switzerland. Beat.Schwaller@unifr.ch
authors.forename: Beat
authors.initials: B
authors.lastname: Schwaller
mesh_terms: D000818:Animals; D064092:Calbindin 1; D064032:Calbindin 2; D064026:Calbindins; D020013:Calcium Signaling; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008931:Mitochondria, Muscle / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D010320:Parvalbumins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D010641:Phenotype; D064030:S100 Calcium Binding Protein G / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
chemical_list: C576498:CALB1 protein, human; C576764:CALB2 protein, human; C576499:Calb1 protein, mouse; C576511:Calb2 protein, mouse; D064092:Calbindin 1; D064032:Calbindin 2; D064026:Calbindins; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G