BISC 307L 2nd Edition Lecture 3Current LectureSecondary 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 topump 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 cellagainst its concentration gradient. -The only secondary active transporters that do not depend on the Na gradient are the HCO3-/Cl-antiport 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 TransportIn 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, andget 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 crossingof 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 thecell, 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 aroundthe 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 mucus-covered 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 apicalmembrane.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 mechanismis 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 youhave a tendency for fatal lung infection. Thickness also interferes with