Figure 1.

Schematic representation of major calcium channels, pumps, exchangers and sensors in mammalian cells. Ca²⁺ influx is mediated by plasma membrane channels including transient receptor potential (TRP) channels, voltage-gated calcium channels (VGCC), ligand-gated ionotropic P2X receptors, mechanosensitive Piezo channels, and store-operated Ca²⁺ entry pathway mediated by stromal interaction molecule 1 (STIM1) sensor and ORAI1 channels. Distribution of Ca²⁺ against a chemical gradient across cell compartments is regulated by Ca²⁺ pumps including the plasma membrane Ca²⁺-ATPase (PMCA), Sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase (SERCA), and Golgi network secretory pathway Ca²⁺/Mn²⁺-ATPase (SPCA). The endoplasmic reticulum (ER) Ca²⁺ channels include ryanodine receptor (RYR) and inositol 1,4,5-trisphosphate (IP3) receptor (IP3R); the latter is activated by IP3 ligand produced by the plasma membrane G protein-coupled receptor (GPCR) via Gaq and phospholipase C-β (PLCβ) proteins. Two-pore channels (TPC) regulate Ca²⁺ release from the endolysosomal system. Mitochondrial Ca²⁺ levels are controlled by mitochondrial calcium uniporter (MCU) complex, and mitochondrial Na⁺/Ca²⁺ exchanger (NCLX).