The use of transgenic mouse models to reveal the functions of Ca^2 + buffer proteins in excitable cells

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• 作者：Beat Schwaller ; ^{Beat.Schwaller@unifr.ch}
• 关键词：Calcium-binding protein ; Calcium buffer ; Calcium homeostasome ; Parvalbumin ; Calbindin-D28k ; Calretinin
• 刊名：Biochimica et Biophysica Acta (BBA)/General Subjects
• 出版年：2012
• 期刊代码：16_03044165
• 类别：bio
• 出版时间：August, 2012
• 卷：1820
• 期：8
• 页码：1294-1303
• 文件大小：283 K

摘要

Background

Cytosolic Ca^2 + buffers are members of the large family of Ca^2 +-binding proteins and are essential components of the Ca^2 + signaling toolkit implicated in the precise regulation of intracellular Ca^2 + signals. Their physiological role in excitable cells has been investigated in vivo by analyzing the phenotype of mice either lacking one of the Ca^2 + buffers or mice with ectopic expression.

Scope of Review

In this review, results obtained with knockout mice for the three most prominent Ca^2 + buffers, parvalbumin, calbindin-D28k and calretinin are summarized.

Major Conclusions

The absence of Ca^2 + buffers in specific neuron subpopulations, and for parvalbumin additionally in fast-twitch muscles, leads to Ca^2 + buffer-specific changes in intracellular Ca^2 + signals. This affects the excitation-contraction cycle in parvalbumin-deficient muscles, and in Ca^2 + 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 Ca^2 + buffers, but have revealed that the absence of Ca^2 + 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 Ca^2 + buffer knockout mice arises from the direct effect of these proteins on Ca^2 + signaling and moreover from the homeostatic mechanisms induced in these mice. For a better mechanistic understanding of neurological diseases linked to disturbed/altered Ca^2 + signaling, a global view on Ca^2 + 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.