Abstract
A general formulation for both passive and active transmembrane transport is derived from basic thermodynamical principles. The derivation takes into account the energy required for the motion of molecules across membranes, and includes the possibility of modeling asymmetric flow. Transmembrane currents can then be described by the general model in the case of electrogenic flow. As it is desirable in new models, it is possible to derive other well known expressions for transmembrane currents as particular cases of the general formulation. For instance, the conductance-based formulation for current turns out to be a linear approximation of the general formula for current. Also, under suitable assumptions, other formulas for current based on electrodiffusion, like the constant field approximation by Goldman, can also be recovered from the general formulation. The applicability of the general formulations is illustrated first with fits to existing data, and after, with models of transmembrane potential dynamics for pacemaking cardiocytes and neurons. The general formulations presented here provide a common ground for the biophysical study of physiological phenomena that depend on transmembrane transport.
Highlights
One of the most important physiological mechanisms underlying communication within and between cells is the transport of molecules across membranes
The most important changes include (i) expanded the Introduction section with details about the transmembrane transport, (ii) precisions about, and notation additions to the formulas for the energy associated to adenosine triphosphate (ATP) hydrolysis, (iii) an expansion of the Discussion section about the sharpness of the upstroke in the action potential in neurons
To show the application of the formulations discussed earlier, let us build a general model of transmembrane potential dynamics with currents generated by M different electrogenic transport mechanisms
Summary
Any reports and responses or comments on the article can be found at the end of the article. The new version contains edits and comments that take into account the observations made by Reviewers 1 and 2, which can be found in the open review section. The most important changes include (i) expanded the Introduction section with details about the transmembrane transport, (ii) precisions about, and notation additions to the formulas for the energy associated to ATP hydrolysis, (iii) an expansion of the Discussion section about the sharpness of the upstroke in the action potential in neurons. Header lines with physical units have been added to the data files for more clarity. A JuPyTeR notebook has been included as Supplementary File 3. The notebook contains code to generate the figures for the paper
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