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Ca 2+ regulation of the Na + /Ca 2+ exchanger
Author(s) -
chaptal vincent,
mercadobesserer Gabriel,
ottolia michela,
nicoll deborah,
philipson kenneth,
abramson jeff
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.698.1
Subject(s) - cytosol , sodium calcium exchanger , biophysics , cytoplasm , chemistry , calcium , contraction (grammar) , myocyte , crystallography , biochemistry , microbiology and biotechnology , biology , endocrinology , enzyme , organic chemistry
Ca 2+ is an essential ion involved in a multitude of processes essential for life. In the heart, Ca 2+ influx into the cytosol leads to muscle contraction. In order for the heart to function properly, the same amount of Ca 2+ entering the cytosol must be removed, to allow the heart to relax and refill with blood. Defects in Ca 2+ cycling result in smaller and slower calcium transients that are characteristic of heart failure. The Na + /Ca 2+ exchanger (NCX1.1) serves as the major mechanism for Ca 2+ extrusion from the myocyte, utilizing the Na + electrochemical gradient to counter‐transport three Na + into the cell while extruding one Ca 2+ . In addition, NCX1.1 is also regulated by these two ions, although these mechanisms remain incompletely understood. Structurally, NCX1.1 has nine predicted trans membrane helices and a large cytoplasmic loop of approximately 500 residues. This loop contains two Ca 2+ Binding Domains (CBD1 & CBD2) that regulate NCX1.1 activity. We solved the structures of CBD1 and CBD2 using X‐ray crystallography and performed a comprehensive mutational and electrophysiological analysis that shed new light on their crucial role in the regulation of NCX1.1 activity. To learn how regulation occurs, we will explore the interactions of these regulatory Ca 2+ binding domains with each other, as well as with other parts of NCX1.1. This work has been funded by AHA and HFSP.