Fluorescent Ca Indicators Directly Inhibit the Na,K-ATPase and Disrupt Cellular Functions

Overview

Journal Sci Signal

Specialties Cell Biology
Physiology
Science

Date 2018 Feb 1

PMID 29382785

Citations 44

Authors

Nathan A Smith

Benjamin T Kress

Yuan Lu

Devin Chandler-Militello

Abdellatif Benraiss

Maiken Nedergaard

Affiliations

Soon will be listed here.

Abstract

Fluorescent Ca indicators have been essential for the analysis of Ca signaling events in various cell types. We showed that chemical Ca indicators, but not a genetically encoded Ca indicator, potently suppressed the activity of Na- and K-dependent adenosine triphosphatase (Na,K-ATPase), independently of their Ca chelating activity. Loading of commonly used Ca indicators, including Fluo-4 acetoxymethyl (AM), Rhod-2 AM, and Fura-2 AM, and of the Ca chelator BAPTA AM into cultured mouse or human neurons, astrocytes, cardiomyocytes, or kidney proximal tubule epithelial cells suppressed Na,K-ATPase activity by 30 to 80%. Ca indicators also suppressed the agonist-induced activation of the Na,K-ATPase, altered metabolic status, and caused a dose-dependent loss of cell viability. Loading of Ca indicators into mice, which is carried out for two-photon imaging, markedly altered brain extracellular concentrations of K and ATP. These results suggest that a critical review of data obtained with chemical Ca indicators may be necessary.

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