Channelrhodopsins

Channelrhodopsins are light-gated ion channels belonging to the microbial rhodopsin family, originally identified in the green alga Chlamydomonas reinhardtii. When illuminated with blue light, channelrhodopsins open to allow cations such as Na+, K+, and Ca2+ to pass, producing an inward current that depolarizes the cell. They are seven-transmembrane proteins with retinal as a chromophore bound to a conserved lysine, and they operate via a photoisomerization-driven conformational change that opens and closes the ion-conducting pore.

Discovered and characterized in the early 2000s, the best known member is Channelrhodopsin-2 (ChR2). It enabled rapid, reversible control of neuronal activity with light and catalyzed the development of optogenetics. Since then, a family of channelrhodopsins and engineered variants has expanded the toolkit, improving spectra, kinetics, and expression. Blue-light–activated ChR2 and its faster derivatives (such as Chronos and the ChETA/ChIEF line) provide millisecond-scale excitation, while red-shifted variants (e.g., Chrimson family) offer deeper tissue penetration and compatibility with other tools.

Applications and impact: Channelrhodopsins enable precise, temporally restricted activation of neurons and other excitable cells, supporting circuit dissection, behavior studies, and therapeutic concepts in neuroscience. They are commonly used alongside inhibitory opsins and reporters to dissect neural function.

Limitations and considerations include the need for light delivery to tissue, potential phototoxicity and heating, desensitization with extended stimulation, variable expression and trafficking, and spectral overlap with imaging dyes. Ongoing engineering aims to improve brightness, specificity, and spectral diversity for broader use.