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USC BISC 307L - Membrane Dynamics Part II
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Membrane Dynamics continuedPrimary Active Transport (4)Called Pumps, against electrical or chemical gradientsAntiportsMove two substances in the opposite directionNa+/K+ ATPaseMuscle contraction, conformation change in protein3 sodium ions for one potassiumcontributes to resting membrane potential (electrogenic)H+/K+ ATPaseUniportsPump one kind of ion in one direction across the membraneCa2+ ATPaseH+ ATPaseSecondary Active TransportEnergy given up as a ion moves down its gradient is coupled to and powers the movement of another substance against its gradientUsually Na+ moving against its gradientSecondary because the ATP is directly used to transport Na+ ions but this ATP comes from other ionsInternal Na+ concentration is 15mM (low)Creates an electrical or chemical gradient for sodiumIntracellular K+ is kept high 150mMAntiports4 classes (3Na+/Ca2+, Na+/H+,H+/K+,Cl-/HCO3-)Transport ions in opposite directionsNa+/Ca2+- exchanger (3 Na+ for every Ca2+)Symports4 classestransport ions in the same directionNa+/Cl-, Na+/K+ 2Cl-, K+/Cl-, Na+/Sugars, AAs, NTsSodium dependent glucose transport moves glucose into the cell against its concentration gradient (called SGLUT)secondary active transporter for glucoseTransepithelial Glucose TransportEpithelial cells form the internal lining of hollow organsOn one side of the epithelial cell is lumen called the APICAL sideOn the other side is the extracellular fluid called the BASOLATERAL membraneEpithelial cells are joined to each other near the apical surface by TIGHT JUNCTIONS- restrict the diffusion of material in between the cellsFunction of the cell in taking up glucose and transporting it across the whole cell and across the basolateral side to flow through the bloodTalking about a cell in the kidneyGlucose is filtered out of the bloodIn the intestine we absorb glucose from foodThe molecules that accomplish thisNa+ / K+ pump is the basis that drives this system in the basolateral membranePumps sodium out and potassium inCreates an electrochemical gradient for sodium to enter the cell which moves glucose against its concentration gradient into the cellThen glucose moves down its concentration gradient into the blood through the GLUT transporterImportant mechanism for K+ secretion at the same time into the lumen and out of the bloodUsually an excess of K+ in our body so we must remove itNaCl and H2O Transport in the Lung (& Colon)Lung and colon epitheliaThere is no active transport mechanism for water molecules- always moves passively down its concentration gradient (osmotic gradient)Movement of water is limited due to the hydrophobic nature of membranes so the permeability is low- there must be AQUAPORINS or water channels to increase permeabilitySince there is no active transport for water, the way to move water is to move solutes and create an osmotic gradientImagine we have an epithelial cell of the lungApical surface lines the lumen full of air and layer of mucusCell will achieve the transport of Na+ Cl- and K+ into the cell creating a gradient for H2O to come inThe sodium potassium pump runs this- keeps the Na+ concentration low in the cell and the K+ does not accumulate and moves out againBrings in two chloride concentration with each Na+ so Cl- concentration accumulates and moves across the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) Which is opened when a site on the intracellular side it phosphorylated by campWhen this CFTR channel is open, Cl- moves out passively which creates an electronegativity in the mucus which attracts Na+ down its gradient and this movement of Na+ and Cl- across the apical membrane creates a osmotic gradient across the membrane as wellImportant in maintaining the proper state of hydration of the mucus on the inside of the lung-important that the mucus isn’t too thick or viscousCFTR was discovered when researching Cystic Fibrosis which makes this system nonfunctional and causes a lack of functional CFTR channels in the membraneOccurs in Europeans and Caucasians and is fatal because you cannot provide hydration to your mucus and becomes too thickSame mechanism is used to secrete the fluid that comes out of the pancreas which cannot be too thick eitherWould clog the pancreatic ductColonSame mechanism is used to keep the water concentration of the stoolsCannot be too hard or too soft (diarrhea)Evolutionary significanceSome bacteria that cause diarrhea have evolved to exploit this mechanism of mucus secretionCreate a toxin that over-activates the CFTRMain treatment is simple oral rehydration (water, salt, sugar)Since homozygosity for this is so lethal why isn’t it eliminated?Because the mutation is so frequent and kill humans before their reproductive ageAlso confers heterozygous advantage- balancing selection. Providing protection against certain bacterial diseasesOne hypothesis is resistance to cholera- individuals with only one functional copy of the CFTR in their genome may protect them against cholera and make them less likely to dieAlso typhoid fever,uses CFTR as a receptor to enter the cell.Cannot affect a cell that has a mutated CFTR geneBut this doesn’t match the geographical distribution of this disease and there are historical records of cholera that don’t match up with thisRecent hypotheses say that this CFTR gene protects against some TBBISC 307L 1st Edition Lecture 3Current Lecture Membrane Dynamics continued- Primary Active Transport (4)o Called Pumps, against electrical or chemical gradients Antiports Move two substances in the opposite direction- Na+/K+ ATPaseo Muscle contraction, conformation change inproteino 3 sodium ions for one potassiumo contributes to resting membrane potential (electrogenic)- H+/K+ ATPase Uniports Pump one kind of ion in one direction across the membrane- Ca2+ ATPase- H+ ATPase- Secondary Active Transporto Energy given up as a ion moves down its gradient is coupled to and powers the movement of another substance against its gradiento Usually Na+ moving against its gradiento Secondary because the ATP is directly used to transport Na+ ions but this ATP comes from other ionso Internal Na+ concentration is 15mM (low) Creates an electrical or chemical gradient for sodium o Intracellular K+ is kept high 150mMo Antiports 4 classes (3Na+/Ca2+, Na+/H+,H+/K+,Cl-/HCO3-) Transport ions in opposite directions Na+/Ca2+- exchanger (3 Na+ for every Ca2+)o Symports 4 classes transport ions in the same direction


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