Inositol 1,4,5-triphosphate (IP₃) serves as a second messenger for many neurotransmitters, hormones and growth factors.¹ The binding of IP₃ to its receptor (IP₃R), which is a ligand-gated Ca²⁺ channel, located predominantly at the endoplasmic reticulum, results in a rapid release of Ca²⁺ from intracellular stores.¹

To date, three known isoforms of IP₃R are known (designated IP₃R1, IP₃R2, and IP₃R3) that can work as homotetramers or hetrotetramers. All three receptors have six transmembrane domains and a pore region between TM5 and TM6. The N-terminus as well as the C-terminus face the cytoplasm. Each IP₃R consists of an N-terminal ligand binding domain (LBD) and a C-terminal domain which is linked by a long regulatory domain. The C-terminus is constitutively active, suggesting that the regulatory domain is required in order to maintain the suppression of channel activity.²

IP₃R1 is one of the most important channels responsible for Ca²⁺ release from intracellular stores and was shown to be the predominant isoform expressed in the central nervous system. IP₃R1 is a pivotal player in many neuronal functions, amongst them, neuronal plasticity and neurite extension.³