title: Model of sarcomeric Ca2+ movements, including ATP Ca2+ binding and diffusion, during activation of frog skeletal muscle.
abstract: Cannell and Allen (1984. Biophys. J. 45:913-925) introduced the use of a multi-compartment model to estimate the time course of spread of calcium ions (Ca2+) within a half sarcomere of a frog skeletal muscle fiber activated by an action potential. Under the assumption that the sites of sarcoplasmic reticulum (SR) Ca2+ release are located radially around each myofibril at the Z line, their model calculated the spread of released Ca2+ both along and into the half sarcomere. During diffusion, Ca2+ was assumed to react with metal-binding sites on parvalbumin (a diffusible Ca2+- and Mg2+-binding protein) as well as with fixed sites on troponin. We have developed a similar model, but with several modifications that reflect current knowledge of the myoplasmic environment and SR Ca2+ release. We use a myoplasmic diffusion constant for free Ca2+ that is twofold smaller and an SR Ca2+ release function in response to an action potential that is threefold briefer than used previously. Additionally, our model includes the effects of Ca2+ and Mg2+ binding by adenosine 5'-triphosphate (ATP) and the diffusion of Ca2+-bound ATP (CaATP). Under the assumption that the total myoplasmic concentration of ATP is 8 mM and that the amplitude of SR Ca2+ release is sufficient to drive the peak change in free [Ca2+] (Delta[Ca2+]) to 18 microM (the approximate spatially averaged value that is observed experimentally), our model calculates that (a) the spatially averaged peak increase in [CaATP] is 64 microM; (b) the peak saturation of troponin with Ca2+ is high along the entire thin filament; and (c) the half-width of Delta[Ca2+] is consistent with that observed experimentally. Without ATP, the calculated half-width of spatially averaged Delta[Ca2+] is abnormally brief, and troponin saturation away from the release sites is markedly reduced. We conclude that Ca2+ binding by ATP and diffusion of CaATP make important contributions to the determination of the amplitude and the time course of Delta[Ca2+].
authors.affiliation: Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6085, USA. baylor@mail.med.upenn.edu
authors.forename: S M
authors.initials: SM
authors.lastname: Baylor
authors.forename: S
authors.initials: S
authors.lastname: Hollingworth
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000814:Aniline Compounds; D000818:Animals; D001001:Anura; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics; D002135:Calcium-Binding Proteins / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002451:Cell Compartmentation / Q000502:physiology; D004058:Diffusion; D005456:Fluorescent Dyes; D008954:Models, Biological; D009119:Muscle Contraction / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000201:enzymology; D018482:Muscle, Skeletal / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D012518:Sarcomeres / Q000502:physiology*; D014966:Xanthenes
chemical_list: D000814:Aniline Compounds; D002135:Calcium-Binding Proteins; D005456:Fluorescent Dyes; D014966:Xanthenes; C059715:Fluo-3; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases; D002118:Calcium