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. 2022 Apr 26;12(5):634. doi: 10.3390/biom12050634

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© 2022 by the author.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Calcium channels drive the activation of the NLRP3 inflammasome. Extracellular calcium is sensed by G-coupled protein receptors (GPCR) including calcium sensing receptor (CaSR) and G Protein-Coupled Receptor Class C Group 6 Member A (GPCR6A). This upregulates the phospholipase C (PLC) calcium signal transduction pathway which in turn activates inositol 1,4,5-triphosphate (IP₃) and its receptor (IP₃R) to release calcium into the cytosol. PLC and diacylglyceral (DAG) also activate other channels including transient receptor potential channels (TRPCs) to allow the influx of calcium into the cell. The influx of calcium into the cytosol activates the assembly of the inflammasome, promoting caspase-1 activation and downstream release of mature IL-1β and IL-18. Created with BioRender.com (accessed on 16 February 2022).