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How Does Regulatory Ca²⁺ Regulate the Na⁺-Ca²⁺ Exchanger?

Vincent Chaptal, Gabriel Mercado Besserer, Michela Ottolia, Debora A. Nicoll, Duilio Cascio, Kenneth D. Philipson and Jeff Abramson

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Spatial and temporal regulation of intracellular Ca²⁺ concentrations is a fundamental requirement for life. The mammalian cardiac Na⁺-Ca²⁺ exchanger serves as the main mechanism for Ca²⁺ efflux after heart contraction. Exchange activity is highly regulated by intracellular Ca²⁺, which binds two regulatory domains (CBD1 and CBD2) and triggers the full activity of the exchanger. We solved the X-ray crystallographic structure of CBD2 in the presence and absence of Ca²⁺. Together with mutational analysis of the Ca²⁺ binding sites, this study reveals the crucial role of one of the two bound Ca²⁺ ions and helps propose hypotheses on the mechanism of regulation of the exchanger.

Authors

Vincent Chaptal

Department of Physiology; University of California; Los Angeles, California USA

Gabriel Mercado Besserer

Department of Physiology; University of California; Los Angeles, California USA

Michela Ottolia

Department of Physiology and Cardiovascular Research Laboratories; University of California; Los Angeles, California USA

Debora A. Nicoll

Department of Physiology and Cardiovascular Research Laboratories; University of California; Los Angeles, California USA

Duilio Cascio

3U.S. Department of Energy Institute for Genomics and Proteomics; University of California; Los Angeles, California USA

Kenneth D. Philipson

Department of Physiology, the Cardiovascular Research Laboratories; University of California; Los Angeles, California USA

Jeff Abramson

Department of Physiology; University of California; Los Angeles, California USA

Purchase article for $19

Subscribe to this journal for $79/year