BISC 307L 2nd Edition Lecture 3 Current Lecture Secondary Active Transporters Active transport because ATP is being directly used to transport the sodium ions out of the cell and Secondary because it is the energy given off as the ion usually sodium moves down its electrochemical gradient that is coupled to another ion that is moving against its electrochemical gradients ex Because of the continual action of the Na K pump the most metabolically active molecule in the body internal sodium concentration in most cells is kept low 15ish mM and intracellular potassium is kept high 150mM This creates a strong gradient for sodium inwards and sodium going down its electrochemical gradient is what powers many of these secondary transporters There are 8 kinds of secondary active transporters 4 antiports on the left first one is electrogenic last 3 are electrically neutral 4 symports transport ions substances in the same direction on the right the first two are electrically neutral and use the energy of the sodium gradient created by the Na K ATPase to pump chloride against its electrical gradient and potassium against its concentration gradient inwards On the lower right is the Na dependent symport for sugars amino acids and neurotransmitters One important example of this transporter is sGLUT sodium dependent glucose transporter which moves glucose into the cell against its concentration gradient The only secondary active transporters that do not depend on the Na gradient are the HCO 3 Clantiport and the K Cl symport The symport is driven by the K gradient coupled to bringing Cl out against its chemical gradient and the HCO3 Cl is driven by whichever ion has a gradient Transepithelial Glucose Transport In the kidney tubule plasma is filtered from the blood but it contains small molecules and valuable glucose You don t want to pee the glucose out with the urine so transepithelial glucose transport needs to occur The intestinal epithelium needs to take up glucose from the lumen where the glucose is being digested transport it through the entire cell s cytoplasm and get it out the basolateral into the ECF where it diffuses into the blood so that we can have energy to power metabolism To the left is an epithelial cell which forms the interior lining of hollow organs On one side is the lumen and it is called the apical side The other side of the cell called the basolateral membrane faces the ECF and it passively exchanges with the capillaries of the blood To prevent control the crossing of material between cells the membranes are joined to each other near the apical surface through tight junctions The whole system is powered by the Na K pump in the basolateral membrane which pumps Na out and K in creating the electrochemical gradient for Na to enter the cell This in turn powers the S glut which uses Na coming in to move glucose against its concentration gradient from the lumen into the cell The glucose diffuses passively through the glut transporter in the basolateral membrane into the ECF where it is whisked away by the blood The Na ions that are pumped out of the cell also flow into the blood and are carried away Lastly the K coming in from the blood through the Na K pump does not accumulate in the cell but exits through K channels in the apical membrane This system also effectively moves excess potassium out of the blood into the lumen where it can pass out into the urine or feces NaCl and H2O Transport in the Lung Colon Transport of water and salt across epithelia is something that happens in many epithelia around the body However there is no active transport mechanism for water it moves passively down its concentration gradient through osmosis Because of this cells move solutes first to create an osmotic gradient allowing water to follow Side note Movement of water across membranes is limited by the hydrophobic interior of lipid bilayers To increase permeability cells have aquaporin membrane water channels AQP This is an epithelial cell lining the alveoli of the lung The apical surface faces the mucuscovered lumen of the lung which is full of air The cell wants to transport Na Cl and H2O up out of the blood vessel on the bottom across the cell and out the apical membrane Again the Na K pump keeps this thing running keeping the internal Na concentration low K doesn t simply accumulate inside because there are channels in the basolateral membrane letting it out The NA gradient is used to power the secondary active transporter on the left the Na K 2Cl symport The chloride moves cross the apical membrane down its gradient through a chloride channel called the CFTR cystic fibrosis transmembrane conductance regulator which is open when a site on the intracellular side is phosphorylated by Kinase A mechanism When this channel is open the chloride moves out passively because its been built up inside and that creates a tendency for electronegativity in the mucus which attracts sodium to go down its electrical gradient through the tight junction This movement of Na and Cl creates an osmotic gradient for water to move through the tight junctions and also through aquaporin channels In the lung this mechanism is important for maintaining hydration of the mucus lining the airways This salt and water together with protein secreted by cell forms the mucus that lines the respiratory passages Mucus can t be too thick or else O2 couldn t diffuse across the epithelium and it can t be too viscous if too viscous it could not be moved by the cilia that move the mucus continually out of the depths of the lung toward the pharynx this mechanism is called the mucoscilliary escalator where they can be swallowed or expectorated CFTR channel was discovered through Cystic fibrosis research CF is a genetic disease in which a single gene mutation renders the CFTR nonfunctional It is detected by cell s error correction mechanism and is destroyed intracellularly so individuals completely lack the CFTR in their apical membranes It mostly occurs in Europeans and is fatal life expectancy is shortened 33 years because without a functional chloride channel transport of salt and water can t be achieved in the lungs so the mucus lining the airway is too thick can t be moved by cilia so you have a tendency for fatal lung infection Thickness also interferes with gas exchange This same mechanism is also used to excrete the fluid that comes out of the pancreas and it is also impaired so that it clogs the pancreatic duct leading to