Optogenetic approaches to control Ca²⁺-modulated physiological processes

As a versatile intracellular second messenger, calcium ion (Ca²⁺) regulates a plethora of physiological processes. To achieve precise control over Ca²⁺ signals in living cells and organisms, a set of optogenetic tools have recently been crafted by engineering photosensitive domains into intracellular signaling proteins, G-protein coupled receptors (GPCRs), receptor tyrosine kinases (RTKs), and Ca²⁺ channels. We highlight herein the optogenetic engineering strategies, kinetic properties, advantages and limitations of these genetically-encoded Ca²⁺ channel actuators (GECAs) and modulators. In parallel, we present exemplary applications in both excitable and non-excitable cells and tissues. Furthermore, we briefly discuss potential solutions for wireless optogenetics to accelerate the in vivo applications of GECAs under physiological conditions, with an emphasis on integrating near-infrared (NIR) light-excitable upconversion nanoparticles (UCNPs) and bioluminescence with optogenetics.