Inositol 1,4,5-trisphosphate (IP 3 ) receptors are emerging as key sites for regulation by pro-and anti-apoptotic factors. Induction of apoptosis for 3 h increased mRNA and protein levels of type 1 IP 3 receptors in non-differentiated (ND), but not in differentiated (D) PC12 cells. Inhibitors of the IP 3 R's calcium release-2-aminoethoxydiphenyl borate (2-APB) and xestospongin-completely prevented Bax and caspase-3 mRNA increase after treatment with the apoptosis inducer set (AIK), and this reinforces the importance of IP 3 R1 in the apoptosis of ND PC12 cells. Apoptosis induction not only increases the IP 3 R1 protein, but it also causes formation of IP 3 R1 clusters in the nucleus which most likely result from fusion of the nucleoplasmic reticulum and/or IP 3 R1 translocation to the nucleus. This is quite similar to the observations noted after overexpression of IP 3 R1 in PC12 cells. The amount of IP 3 induced calcium release was higher in control than in AIK-treated cells. From our results we propose that after the apoptosis induction the amount of intranuclear calcium decreased dramatically due to the increase of calcium permeability of the nuclear calcium store vesicles. Therefore, increase of the calcium permeability may result from IP 3 receptors translocation to nuclei that can boost the calcium transport through IP 3 receptors.