Figure 4

CN is associated with Ca ²⁺ dysregulation in astrocytes. (A) In healthy nervous tissue, elevations in intracellular Ca²⁺ are controlled, in part, by Ca²⁺ release channels (e.g., IP3Rs) located on the endoplasmic reticulum membrane. Levels of several different varieties of plasma membrane Ca²⁺ channels, including L-type Ca²⁺ channels are generally low in non-activated astrocytes. (B) Inflammatory mediators, like cytokines and Aβ, cause hyperactivation of CN and its target transcription factors, NFAT and NFΚB. These events cause the transcriptional upregulation of IP3 receptors and mGluRs leading to increased Ca²⁺ transients and/or higher resting levels of cytosolic Ca²⁺. CN may also increase the function of L-type Ca²⁺ channels, which, like CN, are found at higher levels in activated astrocytes.