Effects of aging on inositol 1,4,5-triphosphate-induced Ca2+ release in unfertilized mouse oocytes

We previously demonstrated in the mouse oocyte that in vivo postovulatory a ging significantly suppresses activity of the endoplasmic reticulum (ER) Ca 2+-ATPase (Igarashi et al. 1997. Mol Reprod Dev 48:383-390). We undertook t he present study to further examine the effects of oocyte aging on Ca2+ rel ease from the inositol 1,4,5-triphosphate (InsP(3))sensitive Ca2+ channels of the ER membrane, because not only Ca2+ reuptake, but also Ca2+ release f rom the ER, substantially affect Ca2+ oscillations in fertilized oocytes. A transient increase in cytosolic free Ca2+ concentration ([Ca2+](i)) was in duced by photolysis of caged InsP(3) microinjected into the cytoplasm in bo th fresh (14 hr post hCG) and aged (20 hr or 24 hr post hCG) oocytes, where the maximum rate of increase in [Ca2+](i) significantly decreased in the a ged oocytes. Reduced ER Ca2+ release in the aged oocyte may not be attribut able to aging-related desensitization of the InsP(3)-sensitive Ca2+ channel s in the ER because concentrations of caged InsP(3) for half maximal [Ca2+] (i) increase were identical for fresh and aged oocytes. The peak [Ca2+](i) response following administration of 5 mu M thapsigargin, a specific ER Ca2 +-ATPase inhibitor, was significantly reduced in the aged oocyte, suggestin g reduction of the ER Ca2+ stores. We conclude from these results that redu ction of Ca2+ release from the InsP(3)-sensitive Ca2+ stores in the aged oo cyte arises from depletion of the ER Ca2+ stores with aging. These aging-re lated changes in Ca2+ release and reuptake may account for alterations in C a2+ oscillations in aged fertilized oocytes. Mol. Reprod. Dev. 55:299-306, 2000. (C) 2000 Wiley-Liss, Inc.