Transepithelial Potential Difference in CF

[lemonade90]

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Why is the transepithelial potential difference more negative in CF?

Though more Cl- is being retained in the cell, more Na is sticking with the Cl- to maintain electroneutrality and Na should have a bigger impact on membrane electrical potential than Cl. I would think that the cell would be more depolarized and have a less negative or even positive potential difference.

 

[Phloston]

Why is the transepithelial potential difference more negative in CF?

Though more Cl- is being retained in the cell, more Na is sticking with the Cl- to maintain electroneutrality and Na should have a bigger impact on membrane electrical potential than Cl. I would think that the cell would be more depolarized and have a less negative or even positive potential difference.

That's a good question.

I would think it's because the sodium can be actively pumped out via the 3Na+/2K+-ATPase pump, independent of chloride, when maintaining intracellular K+. Unlike with digoxin (or ouabain), where that pump is inhibited, thereby indirectly reducing activity of the 3Na+/1Ca2+-ATPase, and charge increases within the cell, if chloride is solitarily retained, as with CF, these two pumps can still work in conjunction to maintain an appropriate balance between K+, Na+ and Ca2+, and the charge gradient due to chloride is disrupted due to defective CFTR alone.

 

[lemonade90]

That makes sense. 👍

 

[MrBeauregard]

That's a good question.

I would think it's because the sodium can be actively pumped out via the 3Na+/2K+-ATPase pump, independent of chloride, when maintaining intracellular K+. Unlike with digoxin (or ouabain), where that pump is inhibited, thereby indirectly reducing activity of the 3Na+/1Ca2+-ATPase, and charge increases within the cell, if chloride is solitarily retained, as with CF, these two pumps can still work in conjunction to maintain an appropriate balance between K+, Na+ and Ca2+, and the charge gradient due to chloride is disrupted due to defective CFTR alone.

The mechanism is actually a little bit different.

The transepithelial potential difference (measured between the surface of the respiratory epithelium and the interstitial fluid) is more negative in patients with CF due to increased luminal sodium absorption. In exocrine glands (not sweat glands), the lack of the CFTR channel results in less chloride secretion as well as increased sodium resorption into the cell (due to the loss of tonic inhibition normally exerted on the sodium channel by the CFTR channel; if the CFTR channel is absent, the sodium channel is now no longer inhibited and can resorb more sodium). The increased sodium resorption into the cell actually affects the membrane potential more than the decreased chloride secretion, such that the resulting transpithelial potential difference is more negative (less sodium outside + more sodium inside = larger potential difference).

 

[lemonade90]

The mechanism is actually a little bit different.

The transepithelial potential difference (measured between the surface of the respiratory epithelium and the interstitial fluid) is more negative in patients with CF due to increased luminal sodium absorption. In exocrine glands (not sweat glands), the lack of the CFTR channel results in less chloride secretion as well as increased sodium resorption into the cell (due to the loss of tonic inhibition normally exerted on the sodium channel by the CFTR channel; if the CFTR channel is absent, the sodium channel is now no longer inhibited and can resorb more sodium). The increased sodium resorption into the cell actually affects the membrane potential more than the decreased chloride secretion, such that the resulting transpithelial potential difference is more negative (less sodium outside + more sodium inside = larger potential difference).

That was similar to explanation I read in UWORLD but if more sodium is in the cell, then why isn't the cell more positive similar to how depolarization happens in cardiac or neuro tissue? I would be able to understand this explanation if Cl and Na were retained in the cell and Cl exerted the more dominant effect on membrane potential but it is Na (more than Cl but less than K) which typically exerts the dominant effect on membrane potential which is why I was confused as to why the difference was more negative (i.e. the inside of the cell was more negative).

 

[The kitchen sink]

Hey, can someone explain the physiological basis for the Sweat test, starting from normal function of the CTFR to abnormal, thanks!

 

[MrBeauregard]

That was similar to explanation I read in UWORLD but if more sodium is in the cell, then why isn't the cell more positive similar to how depolarization happens in cardiac or neuro tissue? I would be able to understand this explanation if Cl and Na were retained in the cell and Cl exerted the more dominant effect on membrane potential but it is Na (more than Cl but less than K) which typically exerts the dominant effect on membrane potential which is why I was confused as to why the difference was more negative (i.e. the inside of the cell was more negative).

The NPD test is measuring the charge on the luminal surface. The increase in sodium resorption results in a loss of positive valences in the bronchial lumen and thus a more negative difference. In patients with normally functioning CFTR channels, the sodium ions stay on the luminal surface, increasing the positive charge and thus decreasing the potential difference.

 

[lemonade90]

The NPD test is measuring the charge on the luminal surface. The increase in sodium resorption results in a loss of positive valences in the bronchial lumen and thus a more negative difference. In patients with normally functioning CFTR channels, the sodium ions stay on the luminal surface, increasing the positive charge and thus decreasing the potential difference.

Makes sense if it is measuring just the luminal charge and NOT transmembrane potential (which I guess would be more positive). I guess when I saw transepithelial I started think of transmembrane potentials.