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

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

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume299
Issue number2
DOIs
StatePublished - Aug 2010

Fingerprint

Smooth Muscle
Aorta
Reticulum
Calcium-Transporting ATPases
Proteins
Adenosine Triphosphatases
Protein Isoforms
Cell Membrane
Transgenes
Myosin Light Chains
sodium-translocating ATPase
Actins
Pharmacology
Messenger RNA

Keywords

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

ASJC Scopus subject areas

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

Cite this

Na+-K+-ATPase and Ca2+ clearance proteins in smooth muscle : A functional unit. / Pritchard, Tracy J.; Bowman, Peggy Sue; Jefferson, Andrew; Tosun, Metiner; Lynch, Ron; Paul, Richard J.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 299, No. 2, 08.2010.

Research output: Contribution to journalArticle

Pritchard, Tracy J. ; Bowman, Peggy Sue ; Jefferson, Andrew ; Tosun, Metiner ; Lynch, Ron ; Paul, Richard J. / Na+-K+-ATPase and Ca2+ clearance proteins in smooth muscle : A functional unit. In: American Journal of Physiology - Heart and Circulatory Physiology. 2010 ; Vol. 299, No. 2.
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