Research ArticleCell Biology

Fluorescent Ca2+ indicators directly inhibit the Na,K-ATPase and disrupt cellular functions

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Sci. Signal.  30 Jan 2018:
Vol. 11, Issue 515, eaal2039
DOI: 10.1126/scisignal.aal2039

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The dark side of tracking Ca2+ in cells

Ca2+ signaling events in many different cell types are tracked with fluorescent Ca2+ indicators, such as Fluo-4, Rhod-2, and Fura-2, and can be inhibited with the Ca2+ chelator BAPTA. Smith et al. found that these commonly used reagents inhibited the Na,K-ATPase, a membrane protein that exchanges intracellular Na+ for extracellular K+ and thus helps set the resting membrane potential and regulate cellular volume. This inhibition, which was accompanied by reduced cell viability, decreased glucose uptake, and cell swelling, occurred in multiple cell types, including neurons, astrocytes, and cardiomyocytes, and in mice when Rhod-2 or Fluo-4 was microdialyzed into the CNS. However, a genetically encoded Ca2+ indicator did not inhibit the Na,K-ATPase. These results suggest that it may be necessary to use these reagents with caution or rely on genetically encoded indicators to prevent cellular toxicity from affecting experimental outcomes.