The Na+/Ca2+-exchanger: An essential component in the mechanism governing cardiac steroid-induced slow Ca2+ oscillations

Tomer Feldmann, Michal Shahar, Akemichi Baba, Toshio Matsuda, David Lichtstein, Haim Rosen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Plasma membrane (PM) Na+, K+-ATPase, plays crucial roles in numerous physiological processes. Cardiac steroids (CS), such as ouabain and bufalin, specifically bind to the Na+, K+-ATPase and affect ionic homeostasis, signal transduction, and endocytosed membrane traffic. CS-like compounds, synthesized in and released from the adrenal gland, are considered a new family of steroid hormones. Previous studies showed that ouabain induces slow Ca2+ oscillations in COS-7 cells by enhancing the interactions between Na+, K+-ATPase, inositol 1,4,5-trisphosphate receptor (IP3R) and Ankyrin B (Ank-B) to form a Ca2+ signaling micro-domain. The activation of this micro-domain, however, is independent of InsP3 generation. Thus, the mechanism underlying the induction of these slow Ca2+ oscillations remained largely unclear. We now show that other CS, such as bufalin, can also induce Ca2+ oscillations. These oscillations depend on extracellular Ca2+ concentrations [Ca2+]out and are inhibited by Ni2+. Furthermore, we found that these slow oscillations are Na+out dependent, abolished by Na+/Ca2+ exchanger1 (NCX1)-specific inhibitors and markedly attenuated by NCX1 siRNA knockdown. Based on these results, a model is presented for the CS-induced slow Ca2+ oscillations in COS-7 cells.

Original languageAmerican English
Pages (from-to)424-432
Number of pages9
JournalCell Calcium
Volume50
Issue number5
DOIs
StatePublished - Nov 2011

Keywords

  • Bufalin
  • COS-7 cells
  • Ouabain

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