Inositol 1,4,5-trisphosphate receptor and ryanodine receptor in the aging brain of Wistar rats.
Intracellular Ca2+ release channels are key players in the regulation of Ca2+ homeostasis. In the present study, we investigated the age-related changes of inositol 1,4,5-trisphosphate (IP3) receptor/Ca2+ release channel and ryanodine receptor/Ca2+ release channel in microsomes derived from either cerebellum or cerebrum cortex from male Wistar rats. A significant reduction (about 50%) in density of IP3 receptor/Ca2+ release channels was observed in cerebrum cortex, only, in 8- and 28-month old rats, whereas density and Kd 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 IP3 receptor, in the cerebrum cortex at least. The relevance of the present findings is discussed in relation to reported changes of neuronal Ca2+ homeostasis during aging.
Centro di Studio per la Biologia e la Fisiopatologia Muscolare del CNR, Dipartimento di Scienze Biomediche Sperimentali, Università di Padova, Italy.
A
A
Martini
F
F
Battaini
S
S
Govoni
P
P
Volpe
D000375:Aging / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002531:Cerebellum / Q000201:enzymology / Q000378:metabolism; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008297:Male; D008861:Microsomes / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009124:Muscle Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D002118:Calcium