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Regulation of Na + ‐K + ATPase (NKA) α‐isoforms and contractility in smooth muscle: evidence from transgenic mice
Author(s) -
Pritchard Tracy J.,
Bullard Daniel P.,
Lynch Ronald M.,
Paul Richard J.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1299-c
Subject(s) - gene isoform , contractility , western blot , medicine , endocrinology , myosin , biology , homeostasis , chemistry , microbiology and biotechnology , biochemistry , gene
NKA is an enzyme that maintains Na + and K + gradients, and coupled to Na + ‐Ca 2+ exchange (NCX), modulates Ca 2+ homeostasis. It has been hypothesized that the α1‐isoform has a “housekeeping” role, whereas the α2‐isoform regulates SR Ca 2+ loading and hence contractility. We developed mice to express either the α1‐ or α2‐isoform (α1 sm+ , α2 sm+ mice) in smooth muscle using the α‐actin promoter, SMP8. Western blot data of aorta and antrum showed that the α1‐isoform was elevated by 1.4‐fold in α1 sm+ mice and the α2‐isoform by 4.7‐7.4‐fold in α2 sm+ 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 α2 sm+ aortic smooth muscle cells were distributed similar to WT. PMCA and NCX were elevated ~5‐fold in α2 sm+ 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 α2 sm+ mice showed altered vascular phenotypes including faster rates of relaxation (95.2 ± 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 Ca 2+ and contractility. Supported by NIH HL66044 (RJP, RML).