Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 736K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Alert me to new content in the JGP Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Baylor, S. M. Articles by Hollingworth, S. Search for Related Content PubMed Articles by Baylor, S. M. Articles by Hollingworth, S. Social Bookmarking                            What's this?

Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104

Correspondence to S.M. Baylor: baylor{at}mail.med.upenn.edu

Ca²⁺ release from the sarcoplasmic reticulum (SR) of skeletal muscle takes place at the triadic junctions; following release, Ca²⁺ spreads within the sarcomere by diffusion. Here, we report multicompartment simulations of changes in sarcomeric Ca²⁺ evoked by action potentials (APs) in fast-twitch fibers of adult mice. The simulations include Ca²⁺ complexation reactions with ATP, troponin, parvalbumin, and the SR Ca²⁺ pump, as well as Ca²⁺ transport by the pump. Results are compared with spatially averaged Ca²⁺ transients measured in mouse fibers with furaptra, a low-affinity, rapidly responding Ca²⁺ indicator. The furaptra f_CaD signal (change in the fraction of the indicator in the Ca²⁺-bound form) evoked by one AP is well simulated under the assumption that SR Ca²⁺ release has a peak of 200–225 µM/ms and a FDHM of 1.6 ms (16°C). f_CaD elicited by a five-shock, 67-Hz train of APs is well simulated under the assumption that in response to APs 2–5, Ca²⁺ release decreases progressively from 0.25 to 0.15 times that elicited by the first AP, a reduction likely due to Ca²⁺ inactivation of Ca²⁺ release. Recovery from inactivation was studied with a two-AP protocol; the amplitude of the second release recovered to >0.9 times that of the first with a rate constant of 7 s^–1. An obvious feature of f_CaD during a five-shock train is a progressive decline in the rate of decay from the individual peaks of f_CaD. According to the simulations, this decline is due to a reduction in available Ca²⁺ binding sites on troponin and parvalbumin. The effects of sarcomere length, the location of the triadic junctions, resting [Ca²⁺], the parvalbumin concentration, and possible uptake of Ca²⁺ by mitochondria were also investigated. Overall, the simulations indicate that this reaction-diffusion model, which was originally developed for Ca²⁺ sparks in frog fibers, works well when adapted to mouse fast-twitch fibers stimulated by APs.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				S. Hollingworth, U. Zeiger, and S. M. Baylor Comparison of the myoplasmic calcium transient elicited by an action potential in intact fibres of mdx and normal mice J. Physiol., November 1, 2008; 586(21): 5063 - 5075. [Abstract] [Full Text] [PDF]

				M. DiFranco, C. E. Woods, J. Capote, and J. L. Vergara Dystrophic skeletal muscle fibers display alterations at the level of calcium microdomains PNAS, September 23, 2008; 105(38): 14698 - 14703. [Abstract] [Full Text] [PDF]

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents