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Effect of aging on calcium signaling in C57Bl6J mouse cerebral arteries

  • Ion Channels, Receptors and Transporters
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Abstract

In cerebral arteries, alterations of vascular reactivity have been observed but not well molecularly characterized. Therefore, we have hypothesized that cerebrovascular reactivity could be modified by aging via a modification of Ca2+ signaling in smooth muscle cells. Ca2+ signals and gene expression implicated in contraction have been measured in posterior and middle cerebral arteries from young (2–3 months) and old (20–22 months) C57Bl6/J mice. Aging induced a decrease of KCl- and caffeine-induced contraction as well as a decrease of the amplitudes and an increase of the durations of KCl- and caffeine-induced Ca2+ signals. These results could be linked with the decrease of gene expression coding for Cav1.2, RyR2, SERCA2, PLB, STIM1, TRIC-B, and the increase of FKBP12.6 and TPCN1 gene expression. Finally, aging induced a modification of InsP3 subtype expression pattern responsible for a modification of the InsP3 affinity to activate Ca2+ signals. These results show that aging induces a decrease of contractility correlated with modifications of the expression of genes encoding Ca2+ signaling toolkit. Globally, the amplitude of Ca2+ signals was decreased, whereas their duration was increased by a defection of Ca2+ store refilling.

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Acknowledgments

CGC has performed RT-qPCR experiments, fluorescent pharmacology, and Ca2+ measurements; CM has performed contraction experiments, supervised experiments, and interpretation of results; and JLM and AP wrote the manuscript. We thank A. Joutel for a helpful discussion; D. Berracochea who gave us old mice to initiate the project; A. Donadieu and N. Biendon for technical assistance; and M. Goillandeau for software development (IMN software facilities). The study was supported by grants from the Centre National des Etudes Spatiales, from CNRS (longevity and aging specific action), and Agence Nationale pour la Recherche (AdapHyG no. ANR-09-BLAN-0148) and Region Aquitaine (CGC doctoral fellowship and confocal microscope).

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Georgeon-Chartier, C., Menguy, C., Prévot, A. et al. Effect of aging on calcium signaling in C57Bl6J mouse cerebral arteries. Pflugers Arch - Eur J Physiol 465, 829–838 (2013). https://doi.org/10.1007/s00424-012-1195-7

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