Physiology 3120 Lecture Notes - Lecture 5: Endocytosis, Juxtaglomerular Cell, Aquaporin 4
9 May 2018
School
Department
Course
Professor
Physiology 3120
Dr. Woods
Lecture 5
Ascending Limb of the loop of Henle
- No water reabsorption, only ion reabsorption
- Main thing that the ascending limb does is reabsorb ions
- Impermeable to water
- When talking about urine concentration, some nephrons have longer loops of henle – its mostly
due to the ascending limb reabsorbing lots of ions
- Ascending limb has a thin portion and a thick portion
- The thin part of the ascending limb has…
o Na+ channel
▪ On the luminal membrane
▪ Reabsorbs Na+ down its concentration gradient
▪ Easy to do bc solutes like Na+ have high concentration in the filtrate compared
to inside of tubule cells
- As you continue to go through the ascending limb of the loop of henle, there are more thick cells
- The thick cells are more metabolically active
- They reabsorb Na+ in a more sophisticated matter – using the Na+, K+, 2Cl- transporter (NKCC2
– this is the only isoform expressed in the kidneys)
- This is also known as the ion multiplier – its an efficient way that the kidney can move many
ions across the membrane bc w one protein conformational change, you are transporting 4 ions
(1 Na+, 1K+, 2Cl-)
- Na+ is the favorable ion (it goes down it concentration gradient)
- Cl- is not favorable bc its moving against an electrical gradient (the inside of cells are more –ive
so it needs to be brought against an electrical gradient) but it can do so bc of the action of Na+
- So we can effectively reabsorb an anion (ex: Cl-) bc its combined with other things that are
favorable (ex: Na+)
- K+ is also unfavorable (its high concentration inside the cell)
- Why is it set up this way? Why would you move 1 thing that is favorable and 3 things that are
not?
o This keeps everything electroneutral – we have 2 +ive ions moving and 2 –ive ions
moving
o There is not a lot of K+ in the filtrate bc its low extracellularly
o In order for the transporter to continue to work, you have to have all of the items
available in the filtrate (you have to have Na+, K+ and Cl-)
o For continued movement of this transporter, we have a K+ leak channel
- K+ leak channel
o In the luminal membrane
o Effectively acts as a recycler of K+
o As soon as the K+ binds to the ion multiplier, and all of the other ions bind, there is a
conformational change, then the K+ can leak back into the filtrate to resupply that
transporter with itself so that the transporter can continue to move
- We also want these items along the basolateral membrane
- K+/Cl- symporter
o On the basolateral side
o K+ is favorable (high concentration inside the cell)
o Cl- uses another molecule (K+) to get moved across the basolateral membrane
- On the luminal side, there is 2 Cl- being moved into the cell for 1 K+
o So in order to prevent a build up of –ive inside the cell, we have Cl- channels on the
basolateral membrane
find more resources at oneclass.com
find more resources at oneclass.com
- Cl- channel
o Cl- is high outside of tubule cell
o So how is Cl- able to move?
o The build up of Cl- concentration within the cell can override the Cl- concentration
outside
o So have favorable electrically movement when Cl- has been building up intracellularly
o We also have an increase in the Cl- composition intracellularly that is just enough to
favor the motion through the Cl- channel through the basolateral membrane
o When this can no longer function bc of the motion of Cl- out, we have a decrease in Cl-
concentration
o Cl- can continue to be reabsorbed bc we have that carrier as well
o So 2 mechanisms to get the Cl- out of the ascending limb cells
- We also have Na+/K+ ATPase on the basolateral membrane
- Which of these transporters are secondary active transporters
o Ion multiplier
o K+/Cl- symporter
- We are not going to talk about hormone regulation that happens at the ascending limb so dw
- Paracellular transport: Na+
o Na+ here is being drived by the –ive charge that is starting to build up in the interstitial
space bc of that Cl-
o As the Cl- is basolaterally transported, we start to increase –ive charge in the interstitial
space, providing Na+ with a favorable charge difference and Na+ will move
- SOOO Na+ can be reabsorbed with a simple channel in the thin cells, ion multiplier in the thick
cells but we also have tight junctions that permit cations like Na+ that can be paracellularly
reabsorbed
Distal Convoluted Tubule
- Think of it as an extension of the ascending limb
- Reabsorbs ions – does NOT reabsorb water
- Note: it is the EARY distal convoluted tubule that acts like the ascending limb so in the EARLY
part of the distal convoluted tubule it is impermeable to water
- Instead of the ion multiplier, we have a Na+/Cl- symporter
o Still able to reabsorb Cl- using the Na+ gradient
- Na+ channel
o Simply reabsorb Na+
o On the luminal membrane
- Na+/K+ ATPase
o On basolateral membrane
- Ca2+ channel
o On the luminal membrane
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Main thing that the ascending limb does is reabsorb ions. When talking about urine concentration, some nephrons have longer loops of henle its mostly. The thin part of the ascending limb has . Na+ is the favorable ion (it goes down it concentration gradient) ions across the membrane bc w one protein conformational change, you are transporting 4 ions (1 na+, 1k+, 2cl-) As you continue to go through the ascending limb of the loop of henle, there are more thick cells. The thick cells are more metabolically active. They reabsorb na+ in a more sophisticated matter using the na+, k+, 2cl- transporter (nkcc2. This is the only isoform expressed in the kidneys) This is also known as the ion multiplier its an efficient way that the kidney can move many. So we can effectively reabsorb an anion (ex: cl-) bc its combined with other things that are favorable (ex: na+)
