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Shedding Light on the Na + /Ca 2+ Exchanger
Author(s) -
OTTOLIA MICHELA,
JOHN SCOTT,
XIE YI,
REN XIAOYAN,
PHILIPSON KENNETH D.
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1387.044
Subject(s) - sodium calcium exchanger , biophysics , chemistry , cytoplasm , electrochemical gradient , ionic bonding , ion transporter , contractility , ion exchange , membrane , ion , biochemistry , intracellular , biology , endocrinology , organic chemistry
The Na + /Ca 2+ exchanger (NCX) regulates cardiac contractility by adjusting the amount of Ca 2+ inside myocytes. NCX accomplishes this by using the electrochemical gradient of Na + : during each cycle three Na + ions enter the cell and one Ca 2+ ion is extruded against its gradient. In addition to being transported, cytoplasmic Na + and Ca 2+ ions also regulate exchanger activity. The physiological relevance and molecular processes underlying ionic regulation remain unclear. Also unresolved are the events that regulate NCX trafficking to the membrane and its oligomeric state. This is essential information to interpret structure–function data. The full‐length exchanger was fused to both CFP and YFP, creating active fluorescent exchangers used in FRET experiments to assess both conformational changes associated with ionic regulation and the oligomeric state of NCX. Electrophysiological characterization demonstrates that these constructs behave similarly to the wild‐type (WT) exchanger. We have been able for the first time to monitor conformational changes of the exchanger Ca 2+ ‐binding sitein vivo. These studies provide a better understanding of the molecular properties of the NCX.