Age-associated differential expression of na+,k+-atpase subunit
isoforms in skeletal muscles of f344/bn rats.
Sun, Xiwu, Murali Nagarajan, Philip W. Beesley and Yuk-Chow Ng.
1Department of Pharmacology, The Milton S. Hershey Medical Center,
College of Medicine, The Pennsylvania State University, Hershey, PA,
USA. and 2 Division of Biochemistry, School of Biological Sciences,
Royal Holloway University of London, Egham, Surrey, U.K., and
#present address: Department of Medicine, Division of Cardiothoracic
Surgery, The Milton S. Hershey Medical Center
APStracts 6:0253A, 1999.
Skeletal muscle expresses multiple isoforms of the Na+,K+-ATPase.
Their expression has been shown to be differentially regulated under
pathophysiological conditions. In addition, previous studies suggest
possible age-dependent alterations in Na-K pump function. The present
study tests the hypothesis that advancing age is associated with
altered Na+,K+-ATPase enzyme activity and isoform-specific changes in
expression of the enzyme subunits. Red and white gastrocnemius
(gast), as well as soleus muscle of male F344/BN rats at 6, 18, and
30 months of age were examined. Na+,K+-ATPase activity, measured by
K+-stimulated 3-O-MFPase activity, increased by about 50% in a mixed
gast homogenate from 30 mo compared to 6 and 18 mo rats. Advancing
age was associated with markedly increased (1- and (1-subunit, and
decreased (2- and (2-subunit in red and white gast. In soleus, there
were similar changes in expression of (1- and (2-subunits, but levels
of (1-subunit were unchanged. Functional Na+,K+-ATPase units,
measured by 3H-ouabain binding, undergo muscle-type specific changes.
In red gast, high-affinity ouabain binding sites, which is a measure
of (2-isozyme, increased in 30-mo-old rats despite decreased levels
of (2-subunit. In white gast, by contrast, decreased levels of (2
-subunit were accompanied by decreased high-affinity ouabain binding
sites. Finally, patterns of expression of the four myosin heavy chain
(MHC) isoforms (Type I, IIA, IIX, and IIB) in these muscles are
similar in the three age groups examined. It is concluded that in the
skeletal muscles of F344/BN rats advancing age is associated with
muscle type-specific alterations in Na+,K+-ATPase activity and
patterns of expression of (- and (-subunit isoforms. These changes
apparently occurred without obvious shift in muscle fiber types since
expression of MHC isoforms remained unchanged. Some of the
alternations occurred between middle-age (18 mo) and senescence (30
mo), and therefore may be attributed to aging of skeletal muscle.
Received 23 July 1998; accepted in final form 25 May 1999.
APS Manuscript Number A669-8.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 14 June 1999