Na+-K+-ATPase and Ca2+ clearance proteins in smooth muscle: A functional unit

Tracy J. Pritchard, Peggy Sue Bowman, Andrew Jefferson, Metiner Tosun, Ronald M. Lynch, Richard J. Paul

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


The Na+-K+-ATPase (NKA) can affect intracellular Ca2+ concentration regulation via coupling to the Na +-Ca2+ exchanger and may be important in myogenic tone. We previously reported that in mice carrying a transgene for the NKA α2-isoform in smooth muscle (α2sm+), the α2-isoform protein as well as the α1-isoform (not contained in the transgene) increased to similar degrees (2-7-fold). Aortas from α2sm+ mice relaxed faster from a KCl-induced contraction, hypothesized to be related to more rapid Ca2+ clearance. To elucidate the mechanisms underlying this faster relaxation, we therefore measured the expression and distribution of proteins involved in Ca2+ clearance. Na+-Ca2+ exchanger, sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), and plasma membrane Ca 2+-ATPase (PMCA) proteins were all elevated up to approximately fivefold, whereas actin, myosin light chain, and calponin proteins were not changed in smooth muscle from α2sm+ mice. Interestingly, the corresponding Ca2+ clearance mRNA levels were unchanged. Immunocytochemical data indicate that the Ca2+ clearance proteins are distributed similarly in wild-type and α2sm+ aorta cells. In studies measuring relaxation half-times from a KCl-induced contraction in the presence of pharmacological inhibitors of SERCA and PMCA, we estimated that together these proteins were responsible for ∼60-70% of relaxation in aorta. Moreover, the percent contribution of SERCA and PMCA to relaxation rates in α2sm+ aorta was not significantly different from that in wild-type aorta. The coordinate expressions of NKA and Ca2+ clearance proteins without change in the relative contributions of each individual protein to smooth muscle function suggest that NKA may be but one component of a larger functional Ca2+ clearance system.

Original languageEnglish (US)
Pages (from-to)H548-H556
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number2
StatePublished - Aug 2010


  • Plasma membrane calcium-adenosinetriphosphatase
  • Sarco(endo)plasmic reticulum calcium-adenosinetriphosphatase
  • Sodium-calcium exchanger
  • Transgenic mice

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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