| Title | Extracellular Potassium Dependence of the Na+/K+-ATPase in Cardiac Myocytes; Isoform Specificity and Effect of Phospholemman. | | Author(s) | Han F, Tucker AL, Lingrel JB, Despa S, Bers DM | | Institution | Northwestern University. | | Source | Am J Physiol Cell Physiol 2009 Jul 1. | | Abstract | 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(+)] 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 alpha1 vs. alpha2 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 WT mice (i.e. current due to NKA alpha1) and mice in which the NKA isoforms have swapped ouabain affinities (alpha1 is ouabain-sensitive and alpha2 is ouabain-resistant) to assess current due to NKA alpha2. We found that NKA alpha1 has a higher affinity for external K(+) than NKA alpha2 (K0.5= 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-KO mice (K0.5=2.0 +/-0.2 mM vs. 1.05 +/-0.08 mM). However, PKA activation by isoproterenol (1 microM) did not alter the K0.5 of NKA for external K(+) in WT myocytes. We conclude that (1) NKA alpha1 has higher affinity for K(+) than NKA alpha2 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. Key words: Na/K-ATPase, phospholemman, voltage-clamp, phosphorylation. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19570895 |
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