Proximal Tubule Transport Notes

Tubular transport

Advantages of filtering and then reabsorbing

-only transporters for those essential solutes which must be recovered are required- less than what is needed if adapted to excrete waste

-water balance is facilitated by using reabsorptive process for H20 rather than secretory one-energetically advantageous as many other solutes can be recovered in association with reabsorption of sodium

-Reabsorption of solutes along the renal tubule based on the Ussing model- dual membrane model created by tight junctions: Basolateral surface has Na/K ATPase, K channels- recycling K+ , apical membrane has a very high permeability to sodium- allows for vectorial transport- tight epithelium

-leaky epithelium- large amount of cotransport, antiport carrier proteins found on apical membrane that are coupled to Na+ influx down electrochemical gradient set by Na/K ATPase-Evidence: Increase in sodium reasborption, leads to increase in oxygen consumpation

Role of different nephron segments

PROXIMAL TUBULE STRUCTURE- BULK REABSORPTION

-Split into three sections : S1, S2, S3- S1 and S2 (convulted tubule), S3 (straight)

-Epithelia- polarised by prescence of tight junctions, asymmetric distribution of cotransport proteins and channels results in vectorial transport

-Brush border microvilli on the apical membrane- increase surface area for reabsorption, allows more cotransport proteins to be packed on the surface , one cell type

-Large amounts of mitochondria, microfilaments

-Leaky epithelium

-High permeability to ions through the paracellular pathway, low transepithelial potential difference

-High water permeability due to prescence of large number of aquaporins

-Reabsorption is isotonic- there is never an osmotic gradient present, as solute moves in water also follows due to high permeability- the sodium concentration in the reabsorbate is the same as that in the plasma-Experiment: Stationary microperfusion technique- solutions of various Na+ conc were entered into the proximal tubule lumen of amphibian proximal tubules- ratio of Na flow and rate of fluid reabsorption are constant and is equal to osmolality of lumen

Mechanism of bulk reabsorption

There are two transport route: Transcellular and paracellular

i) First half of the proximal tubule

-Na+ uptake is coupled with organic solutes (glucose and amino acids), bicarbonate, phosphate through a transcellular route, transported into the cell via Cotransporters

-The chemical driving force for the influx of Na+ is created by the Na/K ATPase pump, 3 Na+ out and 2 K+ in on the basolateral membrane which creates a low concentration gradient of Na+ within the tubular epithelial- this allows Na+ to diffuse down its concentration gradient Evidence: Na+ reabsorption is varied experimentally, and measures renal oxygen consumption- the result is a straight line relationship

-There is also an electrical driving force, as the resting membrane potential of the tubular epithelial cells are -70mv, so the driving force of Na+ = Em-Ena = -70-60mv = -130mv. The main ion that is responsible for setting up the negative resting membrane potential is K+ ions which diffuse out into the interstitium via ROMK K+ channels found on the basolateral membrane

So Na+ transported down the electrochemical gradient

S1 segment some of the Na+ are secreted back into the lumen via the paracellular route due to the transepithelial gradient being -3mv: some animals this contributes to 1/3^rd of the Na+ being reabsorbed

ii) 2^nd Half of proximal tubule

-Na+ uptake is coupled with Cl-

-Paracellular route- where the main driving force is the electrical gradient- in the S1 segment the transepithelial potential difference (lumen to basolateral) is -3mv, resulting in the back leak of Na+ into the lumen (some animals-1/3^rd of the Na+ transported back into the lumen), S3 segment the transepithelial gradient is +3mv (so Na+ reabsorbed)

Transport

a) 1^st half of proximal tubule relies on Na co transportation- transcellular uptake

-variety of cotransporters in the apical membrane that couple downhill uptake of Na+ with the uptake of solutes. Most of the cotransporters are electrogenic and carry a net positive charge into the cell

-Cotransporters exploit the downhill Na+ gradient created by the apical cell membrane, created by Na/K pump in the basolateral membrane. The flux of sodium into the cell is also favoured by the electrically negative cell interior established by K+ channels which also recycles K+

-2/3^rd of the filtered sodium reabsorbed, 100% of the glucose, 99% of the amino acids, majority of HC03-

-The Sodium ions reabsorbed into the cell are extruded into the blood via the Na/K pump or the Na/HC03

Co transporters found in apical membrane

i) Na/Glucose cotransporter (SGLT)

-Couples the movement of D-glucose and Na+ from the lumen to the proximal tubule cell-Phloridzin: inhibits SGLTs

-S1 segment, high capacity/low affinity transporter SGLT2- mediates apical glucose uptake- Na/Glucose stochiomery 1:1

-S3 segment, very low concentrations of glucose present- high affinity/low capacity cotransporter called SGLT1-apical glucose uptake-Na/Glucose stochiometry 2:1, double sodium uptake squares the energy released, so can take glucose against a much steeper concentration

-Once inside the cell glucose exits across the basolateral membrane by a member of GLUT transporters- Na...

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