Effect of aging on calcium signaling in C57Bl6J mouse cerebral arteries.

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 Ca(2+) signaling in smooth muscle cells. Ca(2+) 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 Ca(2+) 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 Ca(2+) signals. These results show that aging induces a decrease of contractility correlated with modifications of the expression of genes encoding Ca(2+) signaling toolkit. Globally, the amplitude of Ca(2+) signals was decreased, whereas their duration was increased by a defection of Ca(2+) store refilling.