| First Author | Despa S | Year | 2012 |
| Journal | Cardiovasc Res | Volume | 95 |
| Issue | 4 | Pages | 480-6 |
| PubMed ID | 22739122 | Mgi Jnum | J:202657 |
| Mgi Id | MGI:5520161 | Doi | 10.1093/cvr/cvs213 |
| Citation | Despa S, et al. (2012) Na(+)/K)+)-ATPase alpha2-isoform preferentially modulates Ca2(+) transients and sarcoplasmic reticulum Ca2(+) release in cardiac myocytes. Cardiovasc Res 95(4):480-6 |
| abstractText | AIMS: Na(+)/K(+)-ATPase (NKA) is essential in regulating [Na(+)](i), and thus cardiac myocyte Ca(2+) and contractility via Na(+)/Ca(2+) exchange. Different NKA-alpha subunit isoforms are present in the heart and may differ functionally, depending on specific membrane localization. In smooth muscle and astrocytes, NKA-alpha2 is located at the junctions with the endo(sarco)plasmic reticulum, where they could regulate local [Na(+)], and indirectly junctional cleft [Ca(2+)]. Whether this model holds for cardiac myocytes is unclear. METHODS AND RESULTS: The ouabain-resistant NKA-alpha1 cannot be selectively blocked to assess its effect. To overcome this, we used mice in which NKA-alpha1 is ouabain sensitive and NKA-alpha2 is ouabain resistant (SWAP mice). We measured the effect of ouabain at low concentration on [Na(+)](i), Ca(2+) transients, and the fractional sarcoplasmic reticulum (SR) Ca(2+) release in cardiac myocytes from wild-type (WT; NKA-alpha2 inhibition) and SWAP mice (selective NKA-alpha1 block). At baseline, Na(+) and Ca(2+) regulations are similar in WT and SWAP mice. For equal levels of total NKA inhibition (~25%), ouabain significantly increased Ca(2+) transients (from DeltaF/F(0)= 1.5 +/- 0.1 to 1.8 +/- 0.1), and fractional SR Ca(2+) release (from 24 +/- 3 to 29 +/- 3%) in WT (NKA-alpha2 block) but not in SWAP myocytes (NKA-alpha1 block). This occurred despite a similar and modest increase in [Na(+)](i) (~2 mM) in both groups. The effect in WT mice was mediated specifically by NKA-alpha2 inhibition because at a similar concentration ouabain had no effect in transgenic mice where both NKA-alpha1 and NKA-alpha2 are ouabain resistant. CONCLUSION: NKA-alpha2 has a more prominent role (vs. NKA-alpha1) in modulating cardiac myocyte SR Ca(2+) release. |
