Skeletal muscle single fiber force production declines early in juvenile male mice with chronic kidney disease

Juvenile mice with early-stage CKD display reduced single fiber contractile function. Cellular force production is lower primarily due to less strongly bound myosin-actin cross-bridges. Additionally, myosin-actin cross-bridge kinetics slow in myosin heavy chain IIA fibers. AbstractChildren with chronic kidney disease (CKD) frequently exhibit delayed physical development and reduced physical performance, presumably due to skeletal muscle dysfunction. However, the cellular and molecular basis of skeletal muscle impairment in juvenile CKD remains poorly understood. Cellular (single fiber) and molecular (myosin-actin interactions and myofilament properties) function was examined ex vivo in slow (soleus) and fast (extensor digitorum longus) contracting muscles of juvenile male (6  weeks old) CKD and control mice. CKD was induced by 0.2% adenine diet for 3 weeks starting at 3 weeks of age. Specific tension (maximal isometric force divided by cross-sectional area) was reduced in larger myosin heavy chain (MHC) I and IIA fibers and in all IIB fibers in juvenile male mice with CKD due to fewer strongly bound myosin-actin cross-bridges. Fiber cross-sectional area in juvenile CKD mice was unchanged in MHC I and IIB fibers and increased in MHC IIA fibers, compared to controls. CKD slowed cross-bridge kinetics (slower rate of myosin force production and longer myosin att achment time,ton) in MHC IIA fibers, and accelerated kinetics (shorterton) in MHC IIB fibers, which may indicate ...
Source: Physiological Reports - Category: Physiology Authors: Tags: ORIGINAL ARTICLE Source Type: research