Computer modelling. Application to studies on the initial rate of Na + uptake by frog skin epidermis

Abstract

In the field of active and passive transport of substances across epithelial membranes little progress has been made, mostly for technical reasons, towards a comprehensive view of a wealth of isolated laboratory data. The present study is an attempt to advance the use of the method of computer simulation, with application of the “Continuous System Modelling Program” into the field of membrane transport. High speed of operation and great versatility make this procedure uniquely suitable to transport studies on multicompartment biological systems, such as epithelia. Basic prerequisites are, a detailed knowledge of the morphological parameters of the system, and an abundance of often isolated laboratory data against which the function of a model membrane can be checked. The simulation process becomes then a study of finding the constraints on all rate constants involved (a few of which may be known) which lead to results compatible with experimental facts. Whereas computer modelling is no substitute for experimental studies, it is one way of arriving at a comprehensive view of the complex flow patterns in such complex structures as epithelia. The computer simulation technique can lead to new, testable predictions, and it gives the laboratory investigator a critical perspective of potential pitfalls in experimental techniques used in studies on fluxes in structures as small as those encountered in epithelia. The usefulness of computer simulation in the field of membrane transport is exemplified by applying it to the problem of the initial rate of uptake of Na + by frog skin epidermis. It is shown, here, that the computer data are in excellent agreement with experimental data on epidermis. Beyond this, the computer data permit calculations on kinetic parameters, e.g. Na + pool sizes and rates of Na + fluxes between compartments, which, for the present at least, cannot be directly measured.