Calcium is known to play a prominent regulatory role in skeletal muscle cells and is amongst others concerned with the activation of contraction and energy production by mitochondria. The latter is either directly or indirectly via elevated concentrations of ATP hydrolysis products . In skeletal muscle cells the ATP turnover rate may increase by as much as 100 fold associated with maximally a 15 kJ/mole drop in ATP free energy.  The primary interest of our research is to investigate the regulation of the energy balance by calcium in relation to the three dimensional skeletal architecture. This muscle architecture is known to differ with muscle cell type, differ within different species and able to adapt to the environment. The most striking difference in skeletal muscle cell architecture is the difference between mammals and amphibians. The ryanodine receptors are located at the A-band I-band junction in all mammalian muscle cells, while in frog they are located in the z-disc region. Other important differences taken into account are the amount of serca pumps at the SR and the number of ryanodine receptors at the terminal cisternae.To explore the effects of the different architectures in skeletal muscle cells a model has been developed, based on the model and calcium measurements on frog skeletal muscle cells from Baylor et al., 1998.  The model focuses on the diffusion of calcium through one myofibril, with calcium influx by a ryanodine receptor, calcium outflux by serca pumps and multiple calcium buffers in the cytoplasm, including troponin C at the actin filaments. The diffusion of calcium and the mobile calcium buffers is modeled using a finite element method. The local calcium concentrations throughout the myofibril are dependent on the positions and densities of the different organelles. The majority of calcium measurements are on a whole cell scale and cannot be applied to measure local calcium concentrations. To compare the model solution with literature calcium data, a spatial average calcium signal is determined from the model. Repositioning of the ryanodine receptors from the z-disc region to the A-I-band junction, results in broader spatial average calcium signals with decreased peak amplitude. Literature data of frog and mouse skeletal muscle cells suggest spatial average calcium signals with similar peak amplitudes.,  The calcium influx of the mammalian myofibril model at the A-I-band junction has been corrected resulting in spatial averaged calcium signals with peak amplitude comparable with the frog skeletal muscle model. Local calcium concentrations in the area of the mitochondria are effected, resulting in higher calcium concentration in mammalian skeletal muscle cells in this area. From these computations, we conclude that mammalian skeletal muscle cell mitochondria are perhaps more regulated by calcium, than in frog muscle.REFERENCES R.A. Meyer and J.M. Foley, Cellular processes integrating the metabolic response to exercise. Handbook of Physiology. Exercise: Regulation and Integration of Multiple Systems. Bethesda, Am. Physiol. Soc, 1996, sect. 12, chapter 18, p. 841-870. S.M. Baylor and S.Hollingworth, Model of sarcomeric Ca2+ movements, including ATP Ca2+ binding and diffusion, during activation of frog skeletal muscle. J Gen Physiol 112:297-316, 1998. S.M. Baylor and S. Hollingworth, Sarcoplasmic reticulum calcium release compared in slow-twitch fibres of mouse skeletal muscle. J Physiol 551:125-138, 2003.
|Title of host publication
|Proceedings of the First Dutch Conference on Bio-Medical Engineering (BME 2007) 18-19 January 2007, Egmond aan zee, The Netherlands
|Place of Publication
|Netherlands, Egmond aan Zee
|Published - 2007