The modelling of a primitive 'sustainable' conservative cell

Abstract

The simple sustainable or 'eternal' cell model, assuming preservation of all proteins, is designed as a building block, a primitive element upon which one can build more complete functional cell models of various types, representing various species. In the modelling we emphasize the electrophysiological aspects, in part because these are a well-developed component of cell models and because membrane potentials and their fluctuations have been generally omitted from metabolically oriented cell models in the past. Fluctuations in membrane potential deserve heightened consideration because probably all cells have negative intracellular potentials and most cells demonstrate electrical activity with vesicular extrusion, receptor occupancy, as well as with stimulated excitation resulting in regenerative depolarization. The emphasis is on the balances of mass, charge, and of chemical species while accounting for substrate uptake, metabolism and metabolite loss from the cell. By starting with a primitive representation we emphasize the conservation ideas. As more advanced models are generated they must adhere to the same basic principles as are required for the most primitive incomplete model.

Figure 1

Diagram of the pumps, leaks and voltage-dependent channels in the cardiac myocyte. (Representing the ionic currents, pumps, and exchanges in the model by Winslow et al. (1999) and from Michailova and McCulloch at the University of California in San Diego, the calcium and magnesium binding to ADP and ATP, to myofilament proteins, and to carrier proteins calsequestrin (inside SR) and calmodulin (cytosolic).) The simple arrows across the membrane are channels; the circles in the membrane are ‘pumps’ when powered by ATP and are exchangers when powered by the transmembrane electrochemical potential differences. Other ionic fluxes in an excitable muscle cell are indicated. Specific action potential models can be found on Web sites. The models of Hodgkin & Huxley (1952), Beeler & Reuter (1977) and Winslow et al. (1999) can be run and parameters changed at http://nsr.bioeng.washington.edu. The Luo–Rudy model is at http://www.bme.jhu.edu/~nthakor/Lab/cardio/isc_mod; the model of DiFrancesco & Noble (1985) is at http://cmrg.ucsd.edu; the Oxsoft model (Noble et al. 1998; Kohl et al. 1999) is at www.oxsoft.co.uk.

Figure 2

Nucleotide and nucleoside reactions in the myocardium. Myocyte and endothelial cells both play a role in regulating the interstitial adenosine concentration and its occupancy of receptors on the smooth muscle cell (from Kroll et al. 1997).