Abstract
The "Virtual Cell" provides a general system for testing cell biological mechanisms and creates a framework for encapsulating the burgeoning knowledge base comprising the distribution and dynamics of intracellular biochemical processes. It approaches the problem by associating biochemical and electrophysiological data describing individual reactions with experimental microscopic image data describing their subcellular localizations. Individual processes are collected within a physical and computational infrastructure that accommodates any molecular mechanism expressible as rate equations or membrane fluxes. An illustration of the method is provided by a dynamic simulation of IP3-mediated Ca2+ release from endoplasmic reticulum in a neuronal cell. The results can be directly compared to experimental observations and provide insight into the role of experimentally inaccessible components of the overall mechanism.
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- Atri A., Amundson J., Clapham D., Sneyd J. A single-pool model for intracellular calcium oscillations and waves in the Xenopus laevis oocyte. Biophys J. 1993 Oct;65(4):1727–1739. doi: 10.1016/S0006-3495(93)81191-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berridge M. J. Inositol trisphosphate and calcium signalling. Nature. 1993 Jan 28;361(6410):315–325. doi: 10.1038/361315a0. [DOI] [PubMed] [Google Scholar]
- Bezprozvanny I., Ehrlich B. E. Inositol (1,4,5)-trisphosphate (InsP3)-gated Ca channels from cerebellum: conduction properties for divalent cations and regulation by intraluminal calcium. J Gen Physiol. 1994 Nov;104(5):821–856. doi: 10.1085/jgp.104.5.821. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bezprozvanny I. Theoretical analysis of calcium wave propagation based on inositol (1,4,5)-trisphosphate (InsP3) receptor functional properties. Cell Calcium. 1994 Sep;16(3):151–166. doi: 10.1016/0143-4160(94)90019-1. [DOI] [PubMed] [Google Scholar]
- Bezprozvanny I., Watras J., Ehrlich B. E. Bell-shaped calcium-response curves of Ins(1,4,5)P3- and calcium-gated channels from endoplasmic reticulum of cerebellum. Nature. 1991 Jun 27;351(6329):751–754. doi: 10.1038/351751a0. [DOI] [PubMed] [Google Scholar]
- Dupont G., Swillens S. Quantal release, incremental detection, and long-period Ca2+ oscillations in a model based on regulatory Ca2+-binding sites along the permeation pathway. Biophys J. 1996 Oct;71(4):1714–1722. doi: 10.1016/S0006-3495(96)79373-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HODGKIN A. L., HUXLEY A. F. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol. 1952 Aug;117(4):500–544. doi: 10.1113/jphysiol.1952.sp004764. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hines M. A program for simulation of nerve equations with branching geometries. Int J Biomed Comput. 1989 Mar;24(1):55–68. doi: 10.1016/0020-7101(89)90007-x. [DOI] [PubMed] [Google Scholar]
- Jafri M. S. A theoretical study of cytosolic calcium waves in Xenopus oocytes. J Theor Biol. 1995 Feb 7;172(3):209–216. doi: 10.1006/jtbi.1995.0017. [DOI] [PubMed] [Google Scholar]
- Jafri M. S., Keizer J. On the roles of Ca2+ diffusion, Ca2+ buffers, and the endoplasmic reticulum in IP3-induced Ca2+ waves. Biophys J. 1995 Nov;69(5):2139–2153. doi: 10.1016/S0006-3495(95)80088-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keizer J., Levine L. Ryanodine receptor adaptation and Ca2+(-)induced Ca2+ release-dependent Ca2+ oscillations. Biophys J. 1996 Dec;71(6):3477–3487. doi: 10.1016/S0006-3495(96)79543-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lytton J., Westlin M., Burk S. E., Shull G. E., MacLennan D. H. Functional comparisons between isoforms of the sarcoplasmic or endoplasmic reticulum family of calcium pumps. J Biol Chem. 1992 Jul 15;267(20):14483–14489. [PubMed] [Google Scholar]
- Monck J. R., Williamson R. E., Rogulja I., Fluharty S. J., Williamson J. R. Angiotensin II effects on the cytosolic free Ca2+ concentration in N1E-115 neuroblastoma cells: kinetic properties of the Ca2+ transient measured in single fura-2-loaded cells. J Neurochem. 1990 Jan;54(1):278–287. doi: 10.1111/j.1471-4159.1990.tb13312.x. [DOI] [PubMed] [Google Scholar]
- Sellers PJ, Dickinson RE, Randall DA, Betts AK, Hall FG, Berry JA, Collatz GJ, Denning AS, Mooney HA, Nobre CA. Modeling the Exchanges of Energy, Water, and Carbon Between Continents and the Atmosphere. Science. 1997 Jan 24;275(5299):502–509. doi: 10.1126/science.275.5299.502. [DOI] [PubMed] [Google Scholar]
- Smith G. D. Analytical steady-state solution to the rapid buffering approximation near an open Ca2+ channel. Biophys J. 1996 Dec;71(6):3064–3072. doi: 10.1016/S0006-3495(96)79500-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith G. D., Wagner J., Keizer J. Validity of the rapid buffering approximation near a point source of calcium ions. Biophys J. 1996 Jun;70(6):2527–2539. doi: 10.1016/S0006-3495(96)79824-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith R. G. NeuronC: a computational language for investigating functional architecture of neural circuits. J Neurosci Methods. 1992 Jul;43(2-3):83–108. doi: 10.1016/0165-0270(92)90019-a. [DOI] [PubMed] [Google Scholar]
- Sneyd J., Keizer J., Sanderson M. J. Mechanisms of calcium oscillations and waves: a quantitative analysis. FASEB J. 1995 Nov;9(14):1463–1472. doi: 10.1096/fasebj.9.14.7589988. [DOI] [PubMed] [Google Scholar]
- Terasaki M., Jaffe L. A. Organization of the sea urchin egg endoplasmic reticulum and its reorganization at fertilization. J Cell Biol. 1991 Sep;114(5):929–940. doi: 10.1083/jcb.114.5.929. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsau Y., Wenner P., O'Donovan M. J., Cohen L. B., Loew L. M., Wuskell J. P. Dye screening and signal-to-noise ratio for retrogradely transported voltage-sensitive dyes. J Neurosci Methods. 1996 Dec 28;70(2):121–129. doi: 10.1016/s0165-0270(96)00109-4. [DOI] [PubMed] [Google Scholar]
- Wang S. S., Thompson S. H. Local positive feedback by calcium in the propagation of intracellular calcium waves. Biophys J. 1995 Nov;69(5):1683–1697. doi: 10.1016/S0006-3495(95)80086-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wu Y. C., Tucker T., Fettiplace R. A theoretical study of calcium microdomains in turtle hair cells. Biophys J. 1996 Nov;71(5):2256–2275. doi: 10.1016/S0006-3495(96)79429-8. [DOI] [PMC free article] [PubMed] [Google Scholar]