Physiology 3120 Lecture Notes - Lecture 4: Distal Convoluted Tubule, Aldosterone, Sodium Channel

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Renal Physiology
Lecture 4
Proximal Tubule
65% of the filtrate is reabsorbed here
Main things reabsorbed:
o Glucose (100%)
o Amino acids
o Ions (K+, Cl-, Na+, Ca2+)
o Water
Na+/K+ ATPase
Located on the basolateral side of membrane of all tubule
segment of nephron
Important in maintaining ion concentration within cells
(Na+ = low; K+ = high)
Na+ conc drives the reabsorption of majority of ions
Regulated by Ang II:
o Improves activity (faster conformational change
more efficient reabsorption)
Na+/glucose
symporter
o Na+ has a favourable gradient; glucose does not
o Conformational change that allows transportation of
both molecule only occurs when both are bound to
protein
o Tubule epithelial cells use the glucose but also have
the task to transport that glucose to rest of the body
o So majority of glucose in these cells are not
phosphorylated and will start to build up
o Once its built up, need to transport out of
basolateral membrane
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Glucose Uniporter
Allow glucose to move out of cell down its concentration
gradient
Na+/AA symporter
Na+ has a favourable gradient; AA does not
20 AA symporter has to recognize all of them (simplified;
most of AA are reabsorbed via this symporter)
AA Uniporter
Allow AA to move out of cell down its concentration
gradient
Na+/H+ Exchanger
Important in balancing the pH of blood
Bicarbonate is another ion that’s filtered in the capsular
space & reabsorbed (bc it is an important buffer)
Reabsorbed via this exchanger
o Bicarbonate binds with H+
o Forms CO2 and H2O
o CO2 is easily absorbed (small non-polar molecule)
Regulated by Ang II
Aquaporin 1
Expressed on the luminal and basal side of membrane
Allow water to move via osmosis into epithelial cells in
response to solutes entering the cell
Followed by movement of water through basolateral
membrane to follow solutes that are being reabsorbed
Example of transcellular transport
Secondary Active
Transport
Don’t use ATP directly, uses Na+ gradient established by the
ATPase to facilitate transport
A more leaky epithelia in proximal tubule (tight junctions expressed here aren’t
very tight)
Allow for molecules to pass through paracellularly (H2O, K+, Cl-)
o K+ Move K+ from lumen to interstitial bc some K+ is being picked up by
the peritubular capillaries to have a more favourable conc gradient
o Cl- Move Cl from lumen to interstitial due to favourable electrochemical
gradient:
As Na+ leaves lumen, it becomes less positive, and lumen is building
up with Cl-
Cl- will follow positive ions paracellularly
High conc in interstitial space but there’s a little reabsorption into
peritubular capillaries
Levels brought down a bit to have a more favourable conc gradient
Clinical Note: Diabetes Mellitus
Urine should not contain glucose
When there is an increased filtered load of glucose, the SGLT transporters (SGLT1 &
SGLT2) can become saturated (as in Diabetes Mellitus), why?
o These are the only protein carriers that are responsible for transporting
glucose
o Prone to saturation and can’t function any faster when this occurs
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