| First Author | Han F | Year | 2009 |
| Journal | Am J Physiol Cell Physiol | Volume | 297 |
| Issue | 3 | Pages | C699-705 |
| PubMed ID | 19570895 | Mgi Jnum | J:152098 |
| Mgi Id | MGI:4356221 | Doi | 10.1152/ajpcell.00063.2009 |
| Citation | Han F, et al. (2009) Extracellular potassium dependence of the Na+-K+-ATPase in cardiac myocytes: isoform specificity and effect of phospholemman. Am J Physiol Cell Physiol 297(3):C699-705 |
| abstractText | Cardiac Na(+)-K(+)-ATPase (NKA) regulates intracellular Na(+), which in turn affects intracellular Ca(2+) and contractility via the Na(+)/Ca(2+) exchanger. Extracellular K(+) concentration ([K(+)]) is a central regulator of NKA activity. Phospholemman (PLM) has recently been recognized as a critical regulator of NKA in the heart. PLM reduces the intracellular Na(+) affinity of NKA, an effect relieved by PLM phosphorylation. Here we tested whether the NKA alpha(1)- vs. alpha(2)- isoforms have different external K(+) sensitivity and whether PLM and PKA activation affects the NKA affinity for K(+) in mouse cardiac myocytes. We measured the external [K(+)] dependence of the pump current generated by the ouabain-resistant NKA isoform in myocytes from wild-type (WT) mice (i.e., current due to NKA-alpha(1)) and mice in which the NKA isoforms have swapped ouabain affinities (alpha(1) is ouabain sensitive and alpha(2) is ouabain resistant) to assess current due to NKA-alpha(2). We found that NKA-alpha(1) has a higher affinity for external K(+) than NKA-alpha(2) [half-maximal pump activation (K(0.5)) = 1.5 +/- 0.1 vs. 2.9 +/- 0.3 mM]. The apparent external K(+) affinity of NKA was significantly lower in myocytes from WT vs. PLM-knockout mice (K(0.5) = 2.0 +/- 0.2 vs. 1.05 +/- 0.08 mM). However, PKA activation by isoproterenol (1 muM) did not alter the K(0.5) of NKA for external K(+) in WT myocytes. We conclude that 1) NKA-alpha(1) has higher affinity for K(+) than NKA-alpha(2) in cardiac myocytes, 2) PLM decreases the apparent external K(+) affinity of NKA, and 3) phosphorylation of PLM at the cytosolic domain does not alter apparent extracellular K(+) affinity of NKA. |
