Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10954411 | Journal of Molecular and Cellular Cardiology | 2005 | 8 Pages |
Abstract
In the mouse, genetic reduction in the Na+, K+-ATPase α1 or α2 isoforms results in different functional phenotypes: heterozygous α2 isolated hearts are hypercontractile, whereas heterozygous α1 hearts are hypocontractile. We examined Na+/Ca2+ exchange (NCX) currents in voltage clamped myocytes (pipette [Na+] = 15 mM) induced by abrupt removal of extracellular Na+. In wild-type (WT) myocytes, peak exchanger currents were 0.59 ± 0.04 pA/pF (mean ± S.E.M., n =1 0). In α1+/- myocytes (α2 isoform increased by 54%), NCX current was reduced to 0.33 ± 0.05 (n = 9, P < 0.001) indicating a lower subsarcolemmal [Na+]. In α2+/- myocytes (α2 isoform reduced by 54%), the NCX current was increased to 0.89 ± 0.11 (n = 8, P = 0.03). The peak sarcolemmal Na+ pump currents activated by abrupt increase in [K+]o to 4 mM in voltage clamped myocytes in which the Na+ pump had been completely inhibited for 5 min by exposure to 0 [K+]o were similar in α1+/- (0.86 ± 0.12, n = 10) and α2+/- myocytes (0.94 ± 0.08 pA/pF, n = 16), and were slightly but insignificantly reduced relative to WT (1.03 ± 0.05, n = 24). The fluo-3 [Ca2+]i transient (F/Fo) in WT myocytes paced at 0.5 Hz was 2.18 ± 0.09, n = 34, was increased in α2+/- myocytes (F/Fo = 2.56 ± 0.14, n = 24, P = 0.02), and was decreased in α1+/- myocytes (F/Fo = 1.93 ± 0.08, n = 28, P < 0.05). Thus the α2 isoform rather than the α1 appears to influence Na+/Ca2+ exchanger currents [Ca2+]i transients, and contractility. This finding is consistent with the proposal that α2 isoform of the Na pump preferentially alters [Na+] in a subsarcolemmal micro-domain adjacent to Na+/Ca2+ exchanger molecules and SR Ca2+ release sites.
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Cell Biology
Authors
Taku Yamamoto, Zhi Su, Amy E. Moseley, Toshie Kadono, John Zhang, Marc Cougnon, Fenghua Li, Jerry B. Lingrel, William H. Barry,