IP₃R1-dependent astrocyte calcium signaling in chronic itch

Astrocytes, the most abundant type of glial cell, are electrically non-excitable cells that use intracellular calcium (Ca²⁺) for functional regulation. Changes in intracellular Ca²⁺ concentration play important roles in the central nervous system (CNS), as they are involved in the release of gliotransmitters and the control of extracellular ion concentrations, thereby affecting the regulation of neuronal excitability, CNS homeostasis, and behavior. Intracellular calcium mobilization in astrocytes is known to be mediated via inositol 1,4,5-trisphosphate receptors (IP₃Rs), particularly IP₃R2, and its association with CNS pathogenesis has been widely reported. In addition, the existence of IP₃R2-independent calcium signaling has recently been postulated; however, the detailed mechanisms and its role in astrocyte functions and CNS pathogenesis are still poorly understood. In this paper, we describe the putative mechanisms underlying IP₃R1-dependent calcium signaling in astrocytes and its effects on the reactive state, compare this signaling with IP₃R2-dependent calcium signaling, and discuss its contribution to chronic itch-like behavior.