title: Improved fatigue resistance in Gsα-deficient and aging mouse skeletal muscles due to adaptive increases in slow fibers.
abstract: Genetically modified mice with deficiency of the G protein α-subunit (G(s)α) in skeletal muscle showed metabolic abnormality with reduced glucose tolerance, low muscle mass, and low contractile force, along with a fast-to-slow-fiber-type switch (Chen M, Feng HZ, Gupta D, Kelleher J, Dickerson KE, Wang J, Hunt D, Jou W, Gavrilova O, Jin JP, Weinstein LS. Am J Physiol Cell Physiol 296: C930-C940, 2009). Here we investigated a hypothesis that the switching to more slow fibers is an adaptive response with specific benefit. The results showed that, corresponding to the switch of myosin isoforms, the thin-filament regulatory proteins troponin T and troponin I both switched to their slow isoforms in the atrophic soleus muscle of 3-mo-old G(s)α-deficient mice. This fiber-type switch involving coordinated changes of both thick- and thin-myofilament proteins progressed in the G(s)α-deficient soleus muscles of 18- to 24-mo-old mice, as reflected by the expression of solely slow isoforms of myosin and troponin. Compared with age-matched controls, G(s)α-deficient soleus muscles with higher proportion of slow fibers exhibited slower contractile and relaxation kinetics and lower developed force, but significantly increased resistance to fatigue, followed by a better recovery. G(s)α-deficient soleus muscles of neonatal and 3-wk-old mice did not show the increase in slow fibers. Therefore, the fast-to-slow-fiber-type switch in G(s)α deficiency at older ages was likely an adaptive response. The benefit of higher fatigue resistance in adaption to metabolic deficiency and aging provides a mechanism to sustain skeletal muscle function in diabetic patients and elderly individuals.
authors.affiliation: Dept. of Physiology, Wayne State Univ. School of Medicine, Detroit, Michigan 48201, USA.
authors.forename: Han-Zhong
authors.initials: HZ
authors.lastname: Feng
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Lee S
authors.initials: LS
authors.lastname: Weinstein
authors.forename: J-P
authors.initials: JP
authors.lastname: Jin
mesh_terms: D000222:Adaptation, Physiological; D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002864:Chromogranins; D004558:Electric Stimulation; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000172:deficiency* / Q000235:genetics; D005838:Genotype; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction; D018763:Muscle Fatigue; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism*; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism*; D009126:Muscle Relaxation; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D010641:Phenotype; D020033:Protein Isoforms; D019210:Troponin I / Q000378:metabolism; D020107:Troponin T / Q000378:metabolism
chemical_list: D002864:Chromogranins; D020033:Protein Isoforms; D019210:Troponin I; D020107:Troponin T; C498642:Gnas protein, mouse; D009218:Myosins; D019205:GTP-Binding Protein alpha Subunits, Gs