title: Parvalbumin gene transfer impairs skeletal muscle contractility in old mice.
abstract: Sarcopenia is the progressive age-related loss of skeletal muscle mass associated with functional impairments that reduce mobility and quality of life. Overt muscle wasting with sarcopenia is usually preceded by a slowing of the rate of relaxation and a reduction in maximum force production. Parvalbumin (PV) is a cytosolic Ca(2+) buffer thought to facilitate relaxation in muscle. We tested the hypothesis that restoration of PV levels in muscles of old mice would increase the magnitude and hasten relaxation of submaximal and maximal force responses. The tibialis anterior (TA) muscles of young (6 month), adult (13 month), and old (26 month) C57BL/6 mice received electroporation-assisted gene transfer of plasmid encoding PV or empty plasmid (pcDNA3.1). Contractile properties of TA muscles were assessed in situ 14 days after transfer. In old mice, muscles with increased PV expression had a 40% slower rate of tetanic force development (p<0.01), and maximum twitch and tetanic force were 22% and 16% lower than control values, respectively (p<0.05). Muscles with increased PV expression from old mice had an 18% lower maximum specific (normalized) force than controls, and absolute force was `26% lower at higher stimulation frequencies (150-300 Hz, p<0.05). In contrast, there was no effect of increased PV expression on TA muscle contractile properties in young and adult mice. The impairments in skeletal muscle function in old mice argue against PV overexpression as a therapeutic strategy for ameliorating aspects of contractile dysfunction with sarcopenia and help clarify directions for therapeutic interventions for age-related changes in skeletal muscle structure and function.
authors.affiliation: Basic and Clinical Myology Laboratory, The University of Melbourne, Melbourne, VIC 3010, Australia.
authors.forename: Kate T
authors.initials: KT
authors.lastname: Murphy
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Ham
authors.forename: Jarrod E
authors.initials: JE
authors.lastname: Church
authors.forename: Timur
authors.initials: T
authors.lastname: Naim
authors.forename: Jennifer
authors.initials: J
authors.lastname: Trieu
authors.forename: David A
authors.initials: DA
authors.lastname: Williams
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Lynch
mesh_terms: D000375:Aging; D000818:Animals; D003600:Cytosol / Q000378:metabolism; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000502:physiology*; D010320:Parvalbumins / Q000235:genetics*; D055948:Sarcopenia / Q000503:physiopathology / Q000628:therapy
chemical_list: D010320:Parvalbumins