title: Can inorganic phosphate explain sag during unfused tetanic contractions of skeletal muscle?
abstract: We test the hypothesis that cytosolic inorganic phosphate (Pi) can account for the contraction-induced reductions in twitch duration which impair summation and cause force to decline (sag) during unfused tetanic contractions of fast-twitch muscle. A five-state model of crossbridge cycling was used to simulate twitch and unfused tetanic contractions. As Piconcentration ([Pi]) was increased from 0 to 30 mmol·L-1, twitch duration decreased, with progressive reductions in sensitivity to Pias [Pi] was increased. When unfused tetani were simulated with rising [Pi], sag was most pronounced when initial [Pi] was low, and when the magnitude of [Pi] increase was large. Fast-twitch extensor digitorum longus (EDL) muscles (sag-prone, typically low basal [Pi]) and slow-twitch soleus muscles (sag-resistant, typically high basal [Pi]) were isolated from 14 female C57BL/6 mice. Muscles were sequentially incubated in solutions containing either glucose or pyruvate to create typical and low Pienvironments, respectively. Twitch duration was greater (P < 0.05) in pyruvate than glucose in both muscles. Stimuli applied at intervals approximately three times the time to peak twitch tension resulted in sag of 35.0 ± 3.7% in glucose and 50.5 ± 1.4% in pyruvate in the EDL (pyruvate > glucose; P < 0.05), and 3.9 ± 0.3% in glucose and 37.8 ± 2.7% in pyruvate in the soleus (pyruvate > glucose; P < 0.05). The influence of Pion crossbridge cycling provides a tenable mechanism for sag. Moreover, the low basal [Pi] in fast-twitch relative to slow-twitch muscle has promise as an explanation for the fiber-type dependency of sag.
authors.affiliation: Human Performance Lab, University of Calgary, Calgary, Alberta, Canada icsmith@ucalgary.ca.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Smith
authors.affiliation: Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Bellissimo
authors.affiliation: Human Performance Lab, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Walter
authors.initials: W
authors.lastname: Herzog
authors.affiliation: Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.
authors.forename: A Russell
authors.initials: AR
authors.lastname: Tupling
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000503:physiopathology*; D010710:Phosphates / Q000378:metabolism* / Q000494:pharmacology; D013742:Tetanus / Q000503:physiopathology*
chemical_list: D010710:Phosphates
keywords: Crossbridge cycling; EDL; fast‐ and slow‐twitch muscle; muscle stimulation; simulated contraction; soleus; twitch kinetics