Figure 5
From: Cortisol modulates calcium release-activated calcium channel gating in fish hepatocytes
A hypothetical model for rapid cortisol stimulation of ([Ca2+]i) in hepatocytes. We propose two modes of action: (1) an indirect effect of cortisol by activating yet unknown membrane receptors to deplete endoplasmic reticulum stores, which then results in the interaction of STIM with ORAI1 to open the CRAC channels causing a biphasic increase in ([Ca2+]i). Our results suggest that PKA-RYR pathway may be more important than the PLC-IP3R pathway in contributing to this indirect cortisol-mediated CRAC channel gating in hepatocytes. (2) A direct effect of cortisol by binding to the ORAI1 and opening the pore to allow extracellular calcium. Based on our molecular simulation, and pharmacological approach, we propose that CRAC channels may act as cortisol-gated ion channels in hepatocytes.
