High resolution

Module 3: Figure InsP3R regulation

Regulation of the inositol 1,4,5-trisphosphate receptor (InsP3R).

Summary of the physiological and pharmacological factors that regulate Ca2+ release by the inositol 1,4,5-trisphosphate receptor (InsP3R). The primary agonists are Ca2+ and InsP3. Adenophostin mimics the action of InsP3. The receptor is also sensitive to reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) and this action can be mimicked by thimerosal. The luminal level of Ca2+ also seems to be important for regulating the sensitivity of the InsP3R (Module 3: Figure InsP3R activation). A number of modulators can influence activity either positively (green arrows) or negatively (red arrows). Some of these phosphorylations are reversed by protein phosphatase 1 (PP1). Channel activity is modulated by phosphorylation through various signalling pathways using messengers such as cyclic AMP, cyclic GMP and PtdIns3,45P3 (PIP3). High levels of Ca2+ inhibit the receptor. There also are a range of pharmacological agents that have been used to inhibit release of Ca2+ by the InsP3R.