title: Passive mechanical properties and related proteins change with botulinum neurotoxin A injection of normal skeletal muscle.
abstract: The effects of botulinum neurotoxin A on the passive mechanical properties of skeletal muscle have not been investigated, but may have significant impact in the treatment of neuromuscular disorders including spasticity. Single fiber and fiber bundle passive mechanical testing was performed on rat muscles treated with botulinum neurotoxin A. Myosin heavy chain and titin composition of single fibers was determined by gel electrophoresis. Muscle collagen content was determined using a hydroxyproline assay. Neurotoxin-treated single fiber passive elastic modulus was reduced compared to control fibers (53.00 kPa vs. 63.43 kPa). Fiber stiffness and slack sarcomere length were also reduced compared to control fibers and myosin heavy chain composition shifted from faster to slower isoforms. Average titin molecular weight increased 1.77% after treatment. Fiber bundle passive elastic modulus increased following treatment (168.83  kPa vs. 75.14 kPa). Bundle stiffness also increased while collagen content per mass of muscle tissue increased 38%. Injection of botulinum neurotoxin A produces an effect on the passive mechanical properties of normal muscle that is opposite to the changes observed in spastic muscles.
authors.affiliation: Department of Bioengineering, University of California and Veterans Administration Medical Centers San Diego, La Jolla, California, USA.
authors.forename: Bryan E
authors.initials: BE
authors.lastname: Thacker
authors.forename: Akihito
authors.initials: A
authors.lastname: Tomiya
authors.forename: Jonah B
authors.initials: JB
authors.lastname: Hulst
authors.forename: Kentaro P
authors.initials: KP
authors.lastname: Suzuki
authors.forename: Shannon N
authors.initials: SN
authors.lastname: Bremner
authors.forename: Randy F
authors.initials: RF
authors.lastname: Gastwirt
authors.forename: Marion L
authors.initials: ML
authors.lastname: Greaser
authors.forename: Richard L
authors.initials: RL
authors.lastname: Lieber
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Ward
mesh_terms: D000818:Animals; D019274:Botulinum Toxins, Type A / Q000494:pharmacology* / Q000627:therapeutic use; D064211:Connectin; D004353:Drug Evaluation, Preclinical; D055119:Elastic Modulus / Q000187:drug effects*; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D009128:Muscle Spasticity / Q000188:drug therapy; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D064211:Connectin; D009124:Muscle Proteins; D020033:Protein Isoforms; D011494:Protein Kinases; D019274:Botulinum Toxins, Type A; D018995:Myosin Heavy Chains