Practice question

Water homeostasis requires rapid equilibration across membranes due to filtration secretion challenges. Simple diffusion through lipid bilayer measurable permeability ten to minus three cm per second insufficient for tissues requiring high flux such as kidney proximal tubule collecting duct reabsorbing one eighty liters per day erythrocytes facing shear retinal epithelium astrocytes buffering potassium via swelling. Aquaporins form family of integral channels forming homotetramers where each monomer twenty eight kilodaltons six transmembrane helices two half helices conserved NPA motifs create constriction allowing single-file water movement up to billion molecules per monomer per second while excluding protons via arginine at ar/R site preserving electrochemical gradients preventing acidification. Transport passive bidirectional following osmotic gradient without ATP hydrolysis or large conformational change like carriers driven by chemical potential. Regulation principally via trafficking vasopressin V2 receptor raising cAMP protein kinase A phosphorylating AQP2 at Ser256 triggering insertion into apical membrane of principal cells increasing reabsorption concentrating urine or gating via loop D phosphorylation pH calcium. Mammals express thirteen isoforms AQP0-12 some aquaglyceroporins AQP3,7,9,10 permeable to glycerol urea. Dysfunction causes nephrogenic diabetes insipidus when water reabsorption fails leading to polyuria.