title: Alterations in slow-twitch muscle phenotype in transgenic mice overexpressing the Ca2+ buffering protein parvalbumin.
abstract: The purpose of this study was to determine whether induced expression of the Ca2+ buffering protein parvalbumin (PV) in slow-twitch fibres would lead to alterations in physiological, biochemical and molecular properties reflective of a fast fibre phenotype. Transgenic (TG) mice were generated that overexpressed PV in slow (type I) muscle fibres. In soleus muscle (SOL; 58 % type I fibres) total PV expression was 2- to 6-fold higher in TG compared to wild-type (WT) mice. Maximum twitch and tetanic tensions were similar in WT and TG but force at subtetanic frequencies (30 and 50 Hz) was reduced in TG SOL. Twitch time-to-peak tension and half-relaxation time were significantly decreased in TG SOL (time-to-peak tension: 39.3 +/- 2.6 vs. 55.1 +/- 4.7 ms; half-relaxation time: 42.1 +/- 3.5 vs. 68.1 +/- 9.6 ms, P < 0.05 for TG vs. WT, respectively; n = 8-10). There was a significant increase in expression of type IIa myosin heavy chain (MHC) and ryanodine receptor at the mRNA level in TG SOL but there were no differences in MHC expression at the protein level and thus no difference in fibre type. Whole muscle succinate dehydrogenase activity was reduced by 12 +/- 0.4 % in TG SOL and single fibre glycerol-3-phosphate dehydrogenase activity was decreased in a subset of type IIa fibres. These differences were associated with a 64 % reduction in calcineurin activity in TG SOL. These data show that overexpression of PV, resulting in decreased calcineurin activity, can alter the functional and metabolic profile of muscle and influence the expression of key marker genes in a predominantly slow-twitch muscle with minimal effects on the expression of muscle contractile proteins.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, NB11.200, Dallas, TX 75235-8573, USA. eva_r_chin@groton.pfizer.com
authors.forename: Eva R
authors.initials: ER
authors.lastname: Chin
authors.forename: Robert W
authors.initials: RW
authors.lastname: Grange
authors.forename: Francois
authors.initials: F
authors.lastname: Viau
authors.forename: Alain R
authors.initials: AR
authors.lastname: Simard
authors.forename: Caroline
authors.initials: C
authors.lastname: Humphries
authors.forename: John
authors.initials: J
authors.lastname: Shelton
authors.forename: Rhonda
authors.initials: R
authors.lastname: Bassel-Duby
authors.forename: R Sanders
authors.initials: RS
authors.lastname: Williams
authors.forename: Robin N
authors.initials: RN
authors.lastname: Michel
mesh_terms: D000818:Animals; D002021:Buffers; D002118:Calcium / Q000378:metabolism*; D000939:Epitopes / Q000235:genetics; D015870:Gene Expression; D006388:Hemagglutinins / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D018657:Muscle Fibers, Slow-Twitch / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D051381:Rats; D016324:Sequence Tagged Sites; D019076:Transgenes
chemical_list: D002021:Buffers; D000939:Epitopes; D006388:Hemagglutinins; D010320:Parvalbumins; D002118:Calcium