Cardiac expression of the Na (+) /Ca (2+) exchanger NCX1 is GATA factor dependent
Nicholas, S.B.; Philipson, K.D.
American Journal of Physiology 277(1): H324-H330
1999
ISSN/ISBN: 0002-9513 PMID: 10409212 Document Number: 500815
The cardiac sarcolemmal Na+/Ca2+ exchanger plays a primary role in Ca2+ efflux and is important in regulating intracellular Ca2+ and beat-to-beat contractility. Of the three Na+/Ca2+ exchanger genes cloned (NCX1, NCX2, and NCX3), only NCX1 is expressed in cardiac myocytes. NCX1 has alternative promoters for heart, kidney, and brain tissue-specific transcripts. Analysis of the cardiac NCX1 promoter (at -336 bp) identified a cardiac-specific minimum promoter (at -137) and two GATA sites (at -75 and -145). In this study, gel shift and supershift analyses identified GATA-4 in primary neonatal cardiac myocytes. Site-directed mutagenesis of the GATA-4 site at -75 abolishes binding and reduces activity of the minimum and full-length promoters by >90 and 30%. Mutation of an E-box at -175 does not alter promoter activity. Reprinted by permission of the publisher.