Physiology 2130 Lecture Notes - Lecture 43: Sodium Channel, Sglt2, Sodium-Glucose Transport Proteins
1 May 2018
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Sodium Reabsorption
● Ion that derive reabsorption through the tubul
● 30x concentration gradient from filtrate to tubule cells
○ High outside of cells
■ Interstitial space (outside of the tube)
■ Filtrate (inside of the tubule)
● Derived from blood plasma
○ Low inside of cells
● Na+ likes to move into the tubule cells
○ But it requires transport (because it is a charged ion)
■ Transporter: protein channel, pore, carrier, etc
● Examples of transporters along the tubule
○ Sodium channels
■ Simple, Na+ can pass through in either direction (usually from the filtrate
into the cell)
■ Ex. ENaC
○ Sodium symporters
■ Binds to sodium but also to other substrates within the filtrate
■ When both the sodium and substrate are bound to the protein, the
conformational change occurs
■ This moves both the sodium and substrate in the SAME direction
● Usually into the cell
■ Ex. sodium-glucose symporter (SGLT)
● A family of proteins
● SGLT-1
○ Move 2 Na+ for 1 glucose molecule
● SGLT-2
○ Moves 1 Na+ for 1 glucose molecule
○ More expressed
○ Major symporter for sodium-glucose in the kidney tubule
■ Still need to have a concentration gradient for this to work
● Usually Na+ is the favourable one
○ Glucose is usually unfavourable
○ Sodium exchangers
■ Moves Na+ and the substrate in OPPOSITE direction (hence exchange)
● Binds to Na+ and substrate on opposite side of the membrane to
induce a conformational change
■ Ex. Na+/H+ exchangers (NHE3)
○ Sodium/Potassium ATPase
■ Maintains the ion concentration differential
● Keeps sodium low and potassium high inside of cell
■ Every epithelial cell will have transporter
find more resources at oneclass.com
find more resources at oneclass.com
● Which membrane it sits on is important to how well it works
Anion Transporter
● Chloride Reabsorption
○ Because it is negative it has additional things to overcome that positive ions do
not
○ Ion reabsorption must remain electroneutral
■ Usually move a positive ion along with a negative ion so that the net
charge movement is zero
○ Chloride is the major anion reabsorbed
● Chloride challenges
○ Transport is against an electrical gradient into tubule cells
■ Inside of the cells are generally negative
○ Transport out of tubule cells must overcome a chemical gradient
■ Chloride concentration is high the interstitial space
● Examples of chloride transporters
○ Chloride channels
■ Only works if there is
○ Chloride symporters
■ NCC
● Movies chloride against its electric/chemical gradient using
another substrates whose movement is favourable
■ Because of chloride’s challenges it is often dragged along with other
substrates
○ Chloride multiporters
■ NKCC2
● Has 2 isoforms, this one is in the kidneys
● Moves 1 sodium, 1 potassium, 2 chloride
Water Reabsorption
● As ions like sodium and chloride are being absorbed in epithelial cells, water would LIKE
to follow
○ Via osmosis
● Can do so only if there are transporters in the membrane for water
○ Need channels, can’t diffuse directly through the membrane
● Water channel
○ Simple diffusion
○ Human genome encodes 4 different aquaporins (I, II, III, IV)
■ AQ II is regulated by ADH
● IMPORTANT
● Can be modified to absorbed or not absorb water by the presence
of ADH
■ AQ I, II, IV are not modified by hormones
● Paracellular water reabsorption
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
30x concentration gradient from filtrate to tubule cells. Na+ likes to move into the tubule cells. But it requires transport (because it is a charged ion) Simple, na+ can pass through in either direction (usually from the filtrate into the cell) Binds to sodium but also to other substrates within the filtrate. When both the sodium and substrate are bound to the protein, the conformational change occurs. This moves both the sodium and substrate in the same direction. Move 2 na+ for 1 glucose molecule. Moves 1 na+ for 1 glucose molecule. Major symporter for sodium-glucose in the kidney tubule. Still need to have a concentration gradient for this to work. Moves na+ and the substrate in opposite direction (hence exchange) Binds to na+ and substrate on opposite side of the membrane to induce a conformational change. Keeps sodium low and potassium high inside of cell. Which membrane it sits on is important to how well it works.
