Abstract
Genetically-encoded calcium indicators (GECI) are indispensable tools for real-time monitoring of intracellular calcium signals and cellular activities in living organisms. Current GECIs are fraught with having sub-optimal peak signal-to-baseline-ratio (SBR) with limited resolution for reporting dynamic calcium transients. We report herein the development of a suite of calcium sensors, designated NEMO, with fast kinetics and ultra-wide dynamic ranges. NEMO indicators report Ca2+ transients with peak SBRs ∼20-fold larger than the top-of-the-range GCaMP series. NEMO further enable the quantification of absolution calcium concentration with ratiometric or photochromic imaging. Compared to GCaMPs, NEMO could detect single action potentials in neurons with peak SBR twice higher and median peak-SBR four times larger in vivo, thereby, outperforming most existing state-of-the-art GECIs. Given their unprecedented high sensitivity and fast resolution for decoding intracellular Ca2+ signals, NEMO sensors may find broad applications in monitoring neuronal activities and other Ca2+-modulated physiological processes.
Competing Interest Statement
The authors have declared no competing interest.
