BISC 307L 1st Edition Lecture 3 Current 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 ATPase o Muscle contraction conformation change in protein o 3 sodium ions for one potassium o 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 Transport o Energy given up as a ion moves down its gradient is coupled to and powers the movement of another substance against its gradient o Usually Na moving against its gradient o Secondary because the ATP is directly used to transport Na ions but this ATP comes from other ions o Internal Na concentration is 15mM low Creates an electrical or chemical gradient for sodium o Intracellular K is kept high 150mM o Antiports o Symports 4 classes 3Na Ca2 Na H H K Cl HCO3 Transport ions in opposite directions Na Ca2 exchanger 3 Na for every Ca2 4 classes transport ions in the same direction Na Cl Na K 2Cl K Cl Na Sugars AAs NTs Sodium dependent glucose transport moves glucose into the cell against its concentration gradient called SGLUT secondary active transporter for glucose Transepithelial Glucose Transport o Epithelial cells form the internal lining of hollow organs On one side of the epithelial cell is lumen called the APICAL side On the other side is the extracellular fluid called the BASOLATERAL membrane Epithelial cells are joined to each other near the apical surface by TIGHT JUNCTIONS restrict the diffusion of material in between the cells o Function of the cell in taking up glucose and transporting it across the whole cell and across the basolateral side to flow through the blood Talking about a cell in the kidney Glucose is filtered out of the blood In the intestine we absorb glucose from food o The molecules that accomplish this Na K pump is the basis that drives this system in the basolateral membrane Pumps sodium out and potassium in Creates an electrochemical gradient for sodium to enter the cell which moves glucose against its concentration gradient into the cell Then glucose moves down its concentration gradient into the blood through the GLUT transporter Important mechanism for K secretion at the same time into the lumen and out of the blood Usually an excess of K in our body so we must remove it NaCl and H2O Transport in the Lung Colon o Lung and colon epithelia o There is no active transport mechanism for water molecules always moves passively down its concentration gradient osmotic gradient o 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 permeability o Since there is no active transport for water the way to move water is to move solutes and create an osmotic gradient o Imagine we have an epithelial cell of the lung Apical surface lines the lumen full of air and layer of mucus Cell will achieve the transport of Na Cl and K into the cell creating a gradient for H2O to come in The sodium potassium pump runs this keeps the Na concentration low in the cell and the K does not accumulate and moves out again Brings in two chloride concentration with each Na so Clconcentration accumulates and moves across the CFTR Cystic Fibrosis Transmembrane Conductance Regulator Which is opened when a site on the intracellular side it phosphorylated by camp When 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 well Important 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 viscous CFTR was discovered when researching Cystic Fibrosis which makes this system nonfunctional and causes a lack of functional CFTR channels in the membrane Occurs in Europeans and Caucasians and is fatal because you cannot provide hydration to your mucus and becomes too thick o Same mechanism is used to secrete the fluid that comes out of the pancreas which cannot be too thick either Would clog the pancreatic duct o Colon Same mechanism is used to keep the water concentration of the stools Cannot be too hard or too soft diarrhea o Evolutionary significance Some bacteria that cause diarrhea have evolved to exploit this mechanism of mucus secretion Create a toxin that over activates the CFTR Main 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 age Also confers heterozygous advantage balancing selection Providing protection against certain bacterial diseases One 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 die Also typhoid fever uses CFTR as a receptor to enter the cell Cannot affect a cell that has a mutated CFTR gene But this doesn t match the geographical distribution of this disease and there are historical records of cholera that don t match up with this Recent hypotheses say that this CFTR gene protects against some TB