Inositol 1,4,5-trisphosphate receptor and ryanodine receptor in the aging brain of Wistar rats

Intracellular Ca 2+ release channels are key players in the regulation of Ca 2+ homeostasis. In the present study, we investigated the age-related changes of inositol 1,4,5-trisphosphate (IP3) receptor⧹Ca 2+ release channel and ryanodine receptor⧹Ca 2+ release channel in microsomes derived from either cerebellum or cerebrum cortex from male Wistar rats. A significant reduction (about 50%) in density of IP 3 receptor⧹Ca 2+ release channels was observed in cerebrum cortex, only, in 8- and 28-month old rats, whereas density and K d of ryanodine binding sites were unaffected in both cerebellum and cerebrum microsomes. These findings, along with impairment of Ca 2+-dependent protein kinase C phosphorylation of endogeneous substrates, point to coordinate, quantitative alterations of both targets of phosphoinositide metabolism, i.e., PKC and IP 3 receptor, in the cerebrum cortex at least. The relevance of the present findings is discussed in relation to reported changes of neuronal Ca 2+ homeostasis during aging.