101_12AI_renal_4_volume_reg_n

101_12AI_renal_4_volume_reg_n - past few lectures, we...

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past few lectures, we learned: 1) we produce a liquid waste called urine 2) we regulate the composition of the blood to retain and maintain what’s optimal 3) we also adjust urine volume to balance fluid loss & intake how can we adjust urine volume today - hormonally regulate water permeability tomorrow - regulate GFR, filtration, reabsorption, & secretion
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how can water move through a cell membrane? 1) recall “water will move if there is an osmotic gradient & a permeability”… 2) therefore, what molecular structure forms this “permeability”? 3) can this permeability be regulated?
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3 guiding principles regarding H 2 O reabsorption H 2 O movement is passive moves from higher to lower concentration rate of H 2 O movement depends on concentration (osmotic) gradient & membrane permeability H 2 O moves thru epithelium mostly via aquaporins (“AQP” = water channels ) wt +aquaporin 20% of normal wt PIP1b (aquaporin) culture medium distilled water 1) wt is impermeable to H 2 O: it doesn’t change shape when osmotic gradient changes 2) if oocyte expresses aquaporin, it swells in distilled H 2 O because H 2 O enters rootlets overgrow in mutant, to support same amount of stems leaves stems rootlets Agre 06 Kaledenhoff 98 unfertilized egg: 1 wild type, 1 injected w AQP1 RNA
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3 guiding principles regarding H 2 O reabsorption H 2 O movement is passive moves from higher to lower concentration rate of H 2 O movement depends on concentration (osmotic) gradient & membrane permeability H 2 O moves thru epithelium mostly via aquaporins (“AQP” = water channels ) where are the aquaporins? how are the osmotic gradients formed? proximal tubule descending L of H ascending L of H distal & collecting tubules P(H 2 O) AQP1 AQP1 none AQP2 AQP3 osmotic gradient reabsorbed salt salt pumped by ascending limb of the loop of Henle; also urea descending limb ascending limb AQP1 AQP1 AQP2 AQP3 none text p.533 AQP2 AQP3
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Murata et al (2000) Nature 407:599 how does H 2 O permeate membranes? look at the structure of AQP1 1) this is a single AQP1, viewed as if you were a H 2 O molecule, looking at a cell membrane, trying to enter or leave the cell. 2) the functional unit is a tetramer: 4 monomers clumped together. 3) each monomer is formed by 269 amino acids [arranged in 6 transmembrane (membrane-spanning ) α 4)
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101_12AI_renal_4_volume_reg_n - past few lectures, we...

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