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In the Thick Ascending Loop of Henle, Paracellular diffusion of certain Solutes like magnesium and calcium takes place. Such diffusion is a result of the positive lumen potential.

Looking at the image above from "Berne & Levy physiology" both sides should produce similar charge when cancelling charges out. I don't understand what exactly produces the positive potential on the lumen side.

I believe the caption attempts to explain it referring to differences in conductivity between the apical and basal membrane but I couldn't understand how they came to the conclusion.

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Don't pay attention to the stoichiometry of the pumps, that will only fool you! The charge is due to passive movement through open channels. This is shown as the "yellow tubes" with dotted lines in the diagram. Students of neuroscience are often confused by a very similar thing, as the resting potential of neurons (as well as voltage during action potentials, for that matter) is determined the same way.

The explanation is in the caption text, quoting from your figure:

Because the apical membrane is conductive primarily to K+, the apical membrane voltage is more negative than the basolateral membrane voltage, which is conductive to K+ and Cl-

The other missing piece of information is that the outside space is (relatively) low in potassium. That means that, given an available path for potassium to diffuse across the membrane, there will be a net flow of potassium out of the cell. That flow causes a negative charge to develop inside, because the potassium diffusing out is positively charged. Very few ions have to actually move to develop a biologically relevant potential (see explanations in other answers involving neurons: https://biology.stackexchange.com/a/76167/27148 and https://biology.stackexchange.com/a/57066/27148), so you can treat the ion concentrations as unchanged (and they will be, out to a fraction of a percentage point) despite this movement.

At some voltage, the negative charge inside the cell will counteract the movement of potassium, so it's not like this is a constant deluge of potassium flowing out, it's more of a maintenance trickle. You can calculate this "reversal/equilibrium voltage" using the Nernst equation.

When you have multiple ion species involved, the equation to use is the Goldman equation which is related to the Nernst equation but involves a relative weighting of different ions by their concentrations and permeabilities. As in the textbook description, adding chloride conductance makes the basolateral membrane less negative than if there was only a potassium conductance, because chloride moves out of the cell as the inside becomes more negative.

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  • $\begingroup$ But what makes the lumen potential positive relative to the extracellular space on the basolateral side? as shown in the image, the paracellular diffusion is driven by that potential difference. yes chloride exits on basolateral side, but looking at the rest of the transporters it seems like the charges should balances out on each side of the cell. Am i missing something? $\endgroup$
    – Omar Shahaltough
    Commented Mar 16, 2022 at 23:27
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    $\begingroup$ @OmarShahaltough Read the explanation in my answer; don't pay attention to the movement shown in the pumps and co-transporters, those don't matter. $\endgroup$
    – Bryan Krause ♦
    Commented Mar 16, 2022 at 23:33
  • $\begingroup$ im sorry if i misunderstood but im not seeming to understand two things: 1. the relevance of the potential inside the cell when it comes to the potential outside of the cell, and 2. What exactly does "makes the basolateral membrane less negative mean"? $\endgroup$
    – Omar Shahaltough
    Commented Mar 17, 2022 at 10:30
  • $\begingroup$ @OmarShahaltough All potentials are relative; the potential inside the membrane and potential outside it are the same, just opposite sign. The apical membrane (left side) has an electrical gradient that is more negative inside, so pulls positive charge in. The basolateral membrane is the one on the right hand side of the diagram; since chloride can move freely on that side, there isn't the same negative gradient into the cell. If you sum these in series, the net result is a pumping of positive ions from the left side through to the right (paracellular diffusion). $\endgroup$
    – Bryan Krause ♦
    Commented Mar 17, 2022 at 13:46

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