Models a two compartment, 1 solute, T1-T2 (facilitated 4-state transporter. Includes binding steps and transmembrane flip rates for free and occupied transporters.
Description
The model is a saturable four state transporter with a binding site on both sides of the membrane for 1 solute in a two compartment model. The binding site undergoes a conformational change, flipping from side 1 to side 2 and back again when it is empty (T1<->T2) or filled (TA1<->TA2).
Equations
4 state transporter between two compartments without flow
where
Surf is the surface area of the membrane,
V1 is the volume of compartment 1,
V2 is the volume of compartment 2,
KdA1 and KdA2 are equilibrium dissociation constants,
konA1 and konA2 are the on rate constants,
koffA1 and koffA2 are the off rate constants,
KT12 is the flip rate for the empty transporter from side 1 to side 2,
KT21 is the flip rate for the empty transporter from side 2 to side 1,
KTA12 is the flip rate for the filled transporter from side 1 to side 2, and
KTA21 is the flip rate for the filled transporter from side 2 to side 1.
WARNING: An additional thermodynamic constraint is not included in the model. For a passive transporter, the transport rate constants should satisfy the following constraint:
The equations for this model may be viewed by running the JSim model applet and clicking on the Source tab at the bottom left of JSim's Run Time graphical user interface. The equations are written in JSim's Mathematical Modeling Language (MML). See the Introduction to MML and the MML Reference Manual. Additional documentation for MML can be found by using the search option at the Physiome home page.
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Klingenberg M. Membrane protein oligomeric structure and transport function. Nature 290: 449-454, 1981. Stein WD. The Movement of Molecules across Cell Membranes. New York: Academic Press, 1967. Stein WD. Transport and Diffusion across Cell Membranes. Orlando, Florida: Academic Press Inc., 1986. Wilbrandt W and Rosenberg T. The concept of carrier transport and its corollaries in pharmacology. Pharmacol Rev 13: 109-183, 1961. Schwartz LM, Bukowski TR, Ploger JD, and Bassingthwaighte JB. Endothelial adenosin transporter characterization in perfused guinea pig hearts. Am J Physiol Heart Circ Physiol 279: H1502-H1511, 2000. Foster DM and Jacquez JA. An analysis of the adequacy of the asymmetric carrier model for sugar transport. Biochim Biophys Acta 436: 210-221, 1976.
Please cite https://www.imagwiki.nibib.nih.gov/physiome in any publication for which this software is used and send one reprint to the address given below:
The National Simulation Resource, Director J. B. Bassingthwaighte, Department of Bioengineering, University of Washington, Seattle WA 98195-5061.
Model development and archiving support at https://www.imagwiki.nibib.nih.gov/physiome provided by the following grants: NIH U01HL122199 Analyzing the Cardiac Power Grid, 09/15/2015 - 05/31/2020, NIH/NIBIB BE08407 Software Integration, JSim and SBW 6/1/09-5/31/13; NIH/NHLBI T15 HL88516-01 Modeling for Heart, Lung and Blood: From Cell to Organ, 4/1/07-3/31/11; NSF BES-0506477 Adaptive Multi-Scale Model Simulation, 8/15/05-7/31/08; NIH/NHLBI R01 HL073598 Core 3: 3D Imaging and Computer Modeling of the Respiratory Tract, 9/1/04-8/31/09; as well as prior support from NIH/NCRR P41 RR01243 Simulation Resource in Circulatory Mass Transport and Exchange, 12/1/1980-11/30/01 and NIH/NIBIB R01 EB001973 JSim: A Simulation Analysis Platform, 3/1/02-2/28/07.