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- Title
Regulation of Na<sup>+</sup>-K<sup>+</sup> ATPase (NKA) α-isoforms and contractility in smooth muscle: evidence from transgenic mice.
- Authors
Pritchard, Tracy J.; Bullard, Daniel P.; Lynch, Ronald M.; Paul, Richard J.
- Abstract
NKA is an enzyme that maintains Na+ and K+ gradients, and coupled to Na+-Ca2+ exchange (NCX), modulates Ca2+ homeostasis. It has been hypothesized that the α1-isoform has a "housekeeping" role, whereas the α2-isoform regulates SR Ca2+ loading and hence contractility. We developed mice to express either the α1- or α2-isoform (α1sm+, α2sm+ mice) in smooth muscle using the α-actin promoter, SMPS. Western blot data of aorta and antrum showed that the α1-isoform was elevated by 1.4-fold in α1sm+ mice and the α2-isoform by 4.7-7.4-fold in α2sm+ mice. Interestingly, in both transgenic lines coordinate upregulation of the opposite isoform was observed at the mRNA and protein levels. Immunomicrographs showed that the α-isoforms in α2sm+ aortic smooth muscle cells were distributed similar to WT. PMCA and NCX were elevated ∼5-fold in α2sm+ mice, but not actin or myosin light chains. The regulatory β-subunit, thought to be expressed in abundance, was elevated with the β1- and β2-isoforms increased by 1.3- and 1.4-fold. The α2sm+ mice showed altered vascular phenotypes including faster rates of relaxation (95.2 a= 8.6 s vs. 119.4 ± 8.2 s, P = 0.06) and lower systolic blood pressure (109.9 ± 1.6 mmHg vs. 121.3 ± 1.4 mmHg, P<0.05). Thus, preliminary evidence suggests that the NKA α-isoforms, NCX, and PMCA may be regulated as a unit in mouse smooth muscle to coordinately regulate Ca2+ and contractility.
- Subjects
SODIUM/POTASSIUM ATPase; SMOOTH muscle; REGULATION of muscle contraction; TRANSGENIC mice; ACTIN; MESSENGER RNA; BLOOD pressure
- Publication
FASEB Journal, 2007, Vol 21, Issue 6, pA1299
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fasebj.21.6.a1299-c