OBJECTIVE: The aim of the present study was to investigate the functional activity and expression of the sarcolemmal Na+/Ca2+-exchanger in the failing human heart. METHODS: Left ventricular samples were taken from eleven patients with end-stage heart failure and six organ donors (normal controls). The Na+/Ca2+-exchanger activity was assessed by measuring Na+ gradient-induced 45Ca2+ transport into sarcolemmal vesicles of quantitatively collected crude membrane preparations. The abundance of the Na+/Ca2+-exchanger protein was determined by Western blot analysis using a specific antiserum and the results were normalized to myocyte specific beta-myosin heavy chain protein content. RESULTS: In membrane preparations of failing human hearts, both the Na+ gradient-induced 45Ca2+ transport activity and the level of immunoreactive Na+/Ca2+-exchanger protein were increased (P < 0.01) by 87% and 160% compared to controls, respectively. CONCLUSIONS: In human end-stage heart failure the increased sarcolemmal Na+/Ca2+-exchanger activity appears to be due to an elevated expression of this protein. An increase in the expression and activity of the Na+/Ca2+-exchanger in the failing human heart may be of important functional significance: while a resulting increase in Ca2+ extrusion across the sarcolemma may limit diastolic Ca2+ overload, a corresponding influx of Na+ may be associated with membrane depolarization and enhanced arrhythmogenesis if the Na+/Ca2+-exchanger operates primarily in the forward mode.
OBJECTIVE: The aim of the present study was to investigate the functional activity and expression of the sarcolemmal Na+/Ca2+-exchanger in the failing human heart. METHODS: Left ventricular samples were taken from eleven patients with end-stage heart failure and six organ donors (normal controls). The Na+/Ca2+-exchanger activity was assessed by measuring Na+ gradient-induced 45Ca2+ transport into sarcolemmal vesicles of quantitatively collected crude membrane preparations. The abundance of the Na+/Ca2+-exchanger protein was determined by Western blot analysis using a specific antiserum and the results were normalized to myocyte specific beta-myosin heavy chain protein content. RESULTS: In membrane preparations of failing human hearts, both the Na+ gradient-induced 45Ca2+ transport activity and the level of immunoreactive Na+/Ca2+-exchanger protein were increased (P < 0.01) by 87% and 160% compared to controls, respectively. CONCLUSIONS: In humanend-stage heart failure the increased sarcolemmal Na+/Ca2+-exchanger activity appears to be due to an elevated expression of this protein. An increase in the expression and activity of the Na+/Ca2+-exchanger in the failing human heart may be of important functional significance: while a resulting increase in Ca2+ extrusion across the sarcolemma may limit diastolic Ca2+ overload, a corresponding influx of Na+ may be associated with membrane depolarization and enhanced arrhythmogenesis if the Na+/Ca2+-exchanger operates primarily in the forward mode.
Authors: Rajan Sah; Rafael J Ramirez; Gavin Y Oudit; Dominica Gidrewicz; Maria G Trivieri; Carsten Zobel; Peter H Backx Journal: J Physiol Date: 2003-01-01 Impact factor: 5.182
Authors: Antonis A Armoundas; Ion A Hobai; Gordon F Tomaselli; Raimond L Winslow; Brian O'Rourke Journal: Circ Res Date: 2003-06-12 Impact factor: 17.367
Authors: B Pieske; M Sütterlin; S Schmidt-Schweda; K Minami; M Meyer; M Olschewski; C Holubarsch; H Just; G Hasenfuss Journal: J Clin Invest Date: 1996-08-01 Impact factor: 14.808
Authors: David P Kao; Brian D Lowes; Edward M Gilbert; Wayne Minobe; L Elaine Epperson; Leslie K Meyer; Debra A Ferguson; Ann Kirkpatrick Volkman; Ronald Zolty; C Douglas Borg; Robert A Quaife; Michael R Bristow Journal: Circ Cardiovasc Genet Date: 2015-01-30