Astrocytic Ca signaling mediated by the endoplasmic reticulum in health and disease.

Astrocytes generate robust intracellular Ca signals that are assumed to be key regulators of astrocytic function. Among various Ca mobilization mechanisms, Ca release from the endoplasmic reticulum (ER) via the inositol 1,4,5-trisphosphate receptor (IPR) has attracted attention as a major component of astrocytic Ca signaling. Manipulation of astrocytic IP-Ca signaling, such as genetic deletion of the type 2 IPR, has revealed multifaceted roles of astrocytic ER Ca release in health and disease. Recent developments in Ca imaging techniques including ER intraluminal Ca imaging have been indispensable in determining the physiological and pathophysiological significance of astrocytic ER Ca release via IPRs. Beneficial and detrimental roles of IPR-dependent Ca release in astrocytes have been revealed in wide variety of disorders in the brain, strongly suggesting astrocytic IP-Ca signaling as a novel and promising therapeutic target.