Chapter 6: Interactions Between Cells and the Extracellular Environment
Chapter 6: Interactions Between Cells and the Extracellular Environment BIOL 3160
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This 12 page Class Notes was uploaded by Olivia Addis on Thursday January 28, 2016. The Class Notes belongs to BIOL 3160 at Clemson University taught by Dr. Tamara McNutt-Scott in Fall 2015. Since its upload, it has received 145 views. For similar materials see Human Physiology in Biological Sciences at Clemson University.
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Date Created: 01/28/16
Chapter 6: Interactions Between Cells and the Extracellular Environment Extracellular Fluid (ECF) – interact with neighboring cells, tissues, and/or organs Cells use ECF to obtain nourishment, release secretions, and eliminate wastes. o Interactions between cells occur through chemical regulators into the extracellular environment. Body Fluids – 2 Compartments Extracellular (33%): blood plasma and interstitial fluid through which there is much exchange. More homogenous than intracellular to accommodate the needs of diverse cells. Intracellular (67%) Fluids are the connection between cells, tissues, and organs. Cells secrete chemical regulators or nutrients that move through the ECM to the target. Extracellular Matrix – connective tissue of tissue/organ Complex network of proteins that are structured specific for a tissue o Interstitial Fluid (IF) with a structural component Functions: scaffolding for cellular attachment and transmits information to regulate activity, migration, growth, and differentiation. ECM is composed of fibrous proteins (collagen and elastin) and a ground substance, which is like a hydrated gel and where the Interstitial Fluid is located o Ground Substance is made up of glyocoproteins and proteoglycans. Glycoproteins are on the surface of the PM and affect interactions between cell and extracellular environment. (EX: integrins) Proteoglycans love to bind water along with other proteins, which helps to create the gel. o Ground substance is a highly functional, complex organization of molecules chemically linked to extracellular protein fibers and glycoproteins of glycocalyx. Provides structural strength to connective tissues. o Integrins are adhesion molecules between cell and ECM to join the intracellular to the extracellular serve to relay signals to integrate them o *Toxins in snake venom block integrinbinding site on platelets, which slows blood clotting. Transport Across the Plasma Membrane The plasma membrane (PM) serves as a “barrier” between extracellular and intracellular compartments PM is selectively permeable, but also has dynamic permeability meaning that it can change in different circumstances to meet the needs of the cell Membrane Transport Processes: o Passive – requires no energy because the net movement of molecules and ions across the PM move from high to low concentration (down the concentration gradient). Diffusion: must be lipidsoluble to flow through PM Facilitated Diffusion: requires a carrier protein o Active – requires energy because the net movement is from low to high concentration (up the concentration gradient). CarrierMediated vs. Transport Without A Carrier o Carrier Mediated: Facilitated Diffusion and Active Transport o NonCarrier: Simple Diffusion (lipidsoluble), diffusion of ions through channel, and diffusion of water through aquaporin channels. Diffusion and Osmosis Molecules of a solution are in constant motion involving s solvent (solution the particle is dissolved in) and a solute (particle). Concentration gradient exists, motion tends to eliminate the difference, with the random motion of molecules is diffusion. o There is movement in both directions despite the concentration gradient, but a net movement from higher to lower occurs until equilibrium is reached. o Mean Diffusion Time: time to reach equilibrium It increases with distance; distances are kept within 100 micrometers for effective change with capillaries. Diffusion Through a PM Nonpolar molecules (O )2or small polar covalent molecules (CO ) w2thout charge can easily move across a PM. It will follow concentration gradient between compartments o Extracellular environment is always oxygenrich as long as there is blood circulation and there is a high concentration of carbondioxide in the cells, which allows gas exchange to occur between cells and the extracellular environment. The opposite process occurs in the lungs. Membrane Channels Charged inorganic ions such as Na and K utilize channels that open the membrane because they cannot flow by diffusion due to their charge. o Channels may be open (diffusion ongoing) or gated. o Particular physiological stimuli opens and closes the gate by ion concentration changes leads to the production of nerve and muscle impulses. o For large, polar molecules, carrier proteins are necessary for their movement across a PM. Rate of Diffusion – speed of diffusion per unit time. J = PA (C o– C)i net flow (J) is directly proportional to the concentration gradient (Co – Ci, the surface are (A) and the membrane permeability coefficient (P) o Greater the P, larger the J is across the PM for any give conc. difference and A. What effects the rate of diffusion? o Magnitude of conc. gradient, diffusing substance’s permeability to PM, temperature, SA available , and distance. Microvilli can inc. apical surface for diffusion to occur at the desired rate. (Ex: small intestine and kidney) Magnitude of a conc. gradient is the driving force for diffusion BUT will not move if PM is not permeable to that molecule. Osmosis – net movement of water across a PM that flows along the concentration gradient (high low) Requires a concentration difference in solutes and the membrane must be impermeable to solute. o If the solute is nonpenetrating, then the water must move so that equilibrium may be met. If these requirements are met, the cell is said to be osmotically active where the solute is “pulling” the water, creating an osmotic pressure. Aquaporins are the water channels through which water can move through the PM. o Sometimes present and sometimes will be inserted into the PM because regulatory molecules have received a stimuli. They serve an import function in the kidneys. Osmotic Pressure (OP) – pressure needed to stop osmosis so that it indicates how strongly a solution draws water. Water is drawn more rapidly with greater solute. o Greater Solute Conc. = Greater OP o OP of pure water = 0 Molarity vs. Molality Molarity: ratio of solute:solvent is not exactly known and the amount of water changes according the to molecular weight of a substance. Molality: better measurement of conc. for osmosis and it is determined with 1 mol of substance in 1 kg of water to compare solutes with the water remaining constant. o This allows us to compare different compartments in the body. o When dealing with osmosis, molality is a more accurate measurement to use. Osmolality – total number of solute per 1L of solution Osmotic pressure depends on the ratio, but not the components of solutes and solvents. o Measured in Osm total molality of a solution Electrolytes will ionize in a solution. Plasma and other fluids have complex osmolality because there are many different organic molecules and electrolytes. o Isosmotic: same osmolality as plasma in the blood Tonicity – change in shape due to volume change, due to the osmotic movement of water. Solute concentration and solute permeability for each solute crossing the PM must be taken into consideration. o Hypoosmotic means lower osmotic pressure than ______. o Hypotonic means less concentration than _______. o Hypertonic means high concentration than ______. Also, higher osmolality and osmotic pressure. Lecture Question: When a cell comes in contact with a solution, hypertonic or hypotonic, the initial concentration of solutes determines the degree of change. o If a cell (300 mOsm) were placed 100 mOsm impermeant solutes, how would its final volume compare to its intial volume? The volume of the cell is going to triple. Homeostasis of Plasma Concentration A variety of mechanisms exist to keep blood plasma osmolality maintained within very narrow limits. o Image on Slide16 of Notes: When a person becomes dehydrated, the blood becomes more concentrated and the total blood volume is reduced. The increase in plasma osmolality and osmotic pressure in the cells of the osmoreceptors in the hypothalamus stimulates them. The hypothalamus is the homeostatic control center so it triggers ADH secretion from the posterior pituitary, which is sent to the kidneys that stimulates it to increase the retention of water. The second line of defense is that the hypothalamus triggers thirst and the organism will drink. The increase in water intake and water retention will raise the blood volume to the set point, then acts as a negative feedback to stop the ADH secretion and feeling of thirst. CARRIERMEDIATED TRANSPORT CarrierMediated Transport Cellular metabolism requires the uptake of organic molecules such as glucose and amino acids, but these molecules are large and polar and cannot cross the PM by simple diffusion; therefore, protein carriers are needed. Carrier proteins exhibit observable characteristics including: o specificity – carriers will only carry a particular molecule(s) o saturation – all transports are being used so that nothing more can be moved Saturation of the carrier proteins means that the rate of transport has reached the transport maximum and is the highest rate. Any more concentration does not matter, the rate will not surpass the transport maximum. This is different than simple diffusion because for diffusion, as the concentration increases, so does the rate of transfer in a linear fashion. There is no transport maximum. o competition – if a carrier can transport more than one, they will compete The molecule that is moved the most would be the molecule in the highest concentration because it has the greatest probability to bind to the carrier protein. Facilitated Diffusion A type of carriermediated transport that moves large molecule like glucose down its concentration gradient, which would mean that it is a passive transport and does not require energy. o It exhibits specificity, competition, and saturation. In the unstimulated state, carrier proteins may be located in the membrane of intracellular vesicles. In response to stimulation to take up more glucose, the vesicle fuses with the PM and the carriers are inserted into the membrane. o Events are dynamic to meet the needs of the cell. Primary Active Transport Active transport is the movement of molecules against their concentration gradient (low high); therefore, it requires energy for carrier function. Primary transport is when hydrolysis of ATP is directly responsible for the function of the carriers. Process: 1. The molecule will bind to its specific carrier at the “recognition site”. 2. Binding stimulates ATP hydrolysis. ATP ADP + P i 3. The P i hosphorylates causes a conformational change in the carrier protein. 4. The carrier protein observes a hingelike motion so that it releases the transported molecule to other side of the PM. Carrier proteins that require ATP are called pumps. NaK Pump The NaK Pump is a very important primary active transport carrier found in all body cells. Intracellular: High K conc. Extracellular: High Na conc. Summary of the process: o 3 Na ions bind to the carrier protein, which then stimulates ATP hydrolysis. This produces a temporary closing of the carrier, and then the ADP is released changing the shape of the protein to allow 3 Na ions to exit into the extracellular fluid. 2 K ions in the extracellular fluid bind to carrier, releasing the Pifrom the carrier. After P is released, the carrier protein is allowed to return to its initial state and the 2 K ions flow into the cytoplasm. Functions that the steep ion gradient provide: o Provide NRG for coupled transport of other molecules o Generates Action Potentials for nervous and muscle tissue o Na movement is important for osmosis If the pump isn’t working, there will be an increase in Na in the cell as it tries to reach equilibrium, which causes osmotic influx of water swelling of cell leading to damage or even bursting Secondary Active Transport It is active transport that is driven indirectly by passive ion gradients created by + operation of primary active pumps. Therefore, ATP+is required to maintain Na concentration gradients so that the flow of Na along its gradient can move another molecule at the same time. (cotransport) + o If the molecule moves the same direction as Na , then it is referred to as symport. o If the molecule moves the opposite direction as Na , then it is referred to as antiport. What happens if the NaK pump is poisoned? o The cell can no longer produce ATP, which maintains the concentration gradient for the NaK pump. As Na comes to equilibrium, the other molecules will cause an effect. Anything utilized will also stop. Transport Across Membranes Movement of solutes involves membrane proteins for facilitated diffusion, ion channels, primary active transport, and secondary active transport. o Can be modulated by various signals, resulting in controlled rise or fall in solute fluxes across PM Regulate how things are moved Dynamic for different needs o Specialized cells may need additional and specific transporters and channels that are optimal for that cells function. Transport Across Epithelial Membranes Epithelial cells line surfaces and cavities so anything entering the body must pass through an epithelial cell layer. Functions of Epithelial Cells: o Absorption is the transport of products from cells into the blood. o Reabsorption is the transport of something originally derived from blood back into blood circulation. o Transcellular transport (across cytoplasm), transepithelial transport (across membrane), transcytosis (movement uses endocytosis or exocytosis) o Paracellular Transport is transport between cells using a junctional complex Polarity, or definite direction of transport through epithelial cells is from apical surface (outer) to basolateral surface (inner). o Movement of Glucose: comes into epithelial cell on apical surface by cotransport with Na moving down its conc. gradient. Then, ATP is used to power the NaK pump that and glucose can move across the basolateral surface down its conc. gradient by facilitated diffusion. (SEE IMAGE ON SLIDE 23 TO SEE THIS PROCESS) Junctional Complex Connect adjacent cells for paracellular transport. It seals off epithelial membrane forcing things to move through the epithelial membrane by selection to regulate what comes in and out of cells, but it also provides the cell with other characteristics. o Presence and number of junctions depend on the location. 3 Structures: o Tight Junction – physically joins and seals 2 adjacent PMs by proteins through them and connecting to the cytoskeleton. Selectively permeable and sometimes even leaky o Adherens (Gap) Junction – “glue” together membranes; attached to cytoskeleton and acts as the belt that upholds the apical surface o Desmosome – Velcroed together with many connections to cytoskeletal elements throughout the basal ends of the cells, through which they help to distribute stress across the lining as to not damage the cells under different circumstances. Bulk Transport – transport of multiple molecules at a time that are too big to be moved through the membrane (EX: polypeptides and proteins) Endocytotic Events move molecules into the cells. o Receptor Mediated: receptors on the surface are activated and the membrane invaginates to pull molecules in, then are released into the cell within a coated vesicle. o Pinocytosis: cell drinking by invagination pulling extracellular fluid into the cell in a vesicle. o Phagocytosis: with “feet” that reach out to grab food to pull it into a food vacuole. Exocytosis secretes molecules out of cells. Vesicle joins into the plasma membrane to secrete cellular product, which then is in the extracellular fluid. MEMBRANE POTENTIAL The Membrane Potential – charges of opposite signs on either side of PM have the potential to do work if allowed to come together. Results from: o Action of NaK pump that creates a concentration gradient and amplifies it since these ions move against their concentration gradient. o Permeability of PM; there is an unequal distribution of charges across PM (only at PM), however, the charge is equal when added up. The PM is more permeable to K and when it goes against its gradient, the PM because less positively charged or negatively charged. Leakage channels for K, but not Na o The presence of impermeant molecule (fixed anions) pull the positively charged cations into the cell. This yields an observed “charge” only at the PM, and is primarily due to the concentration gradient of K Electrical potential is determined by the difference in the amount of charge between 2 points. measured in volts For a cell, the NaK pump and the fixed anions are constant, but the leakage channels are an important variable. Equilibrium Potentials K equilibrium potential, E kis where the K conc. is stable if the membrane was only permeable to K and is 90mv. Na equilibrium potential, E Nais where the Na conc. is stable if the membrane was only permeable to Na and is 66mv. o The main influences on membrane potential are Na , K , Cl, and Ca 2+ Equilibrium potentials helps explain how the PM becomes more permeable at times. o Ex: An excitable cell because nerve impulses will come from membrane potentials. The membrane potential at rest is close to the E Kat 70mv, but a little less because there are other players. o The PM of a neuron will become permeable to Na for a brief period so that the membrane potential moves toward E . This is the start of a action NA potential being produced. Nernst Equation Diffusion gradients of an ion depend on conc. differences, and the equilibrium potential depends on the ratio of concentrations on either side of the PM. The Nernst equation determines the electrical potential necessary to balance a given ion conc. gradient across PM so no net flux of the ion occurs. o It differs between ions for a cation, if the concentration inside is greater than the outside, then the value is negative. 61 is always the constant. z is the valence (charge) X Ois conc. outside X is conc. inside GolmanHodgingKatz equation (V ) m The permeability coefficient (P) accounts for each ions permeability. o K has the highest permeability, which explains why Resting Membrane Potential is close to K . outside and inside reversed for Cl because it is an anion, mvmt. has opposite effect on PM r Resting Membrane Potential (RMP) The potential when in a cell is in its inactivated state. Depends on the ratio of concentrations of each ion and the permeability of each ion. + + 2 Most important players: Na , K , Cl, and Ca o Their contributions are dependent on their conc. differences and permeabilities. Any change in conc. will change the RMP, but only as much as the membrane is permeable to. Change in permeability will also change RMP Na would have the greatest effect because it has the lowest permeability, which is why it plays a big role in excitable cells creating an action potential. Normal RMP range for cells: 65mV to 85mV Lecture Question: Would lowering a neuron’s IC [K] by 1 mM have the same effect on RMP as raising the EC [K] by 1 mM? o No; changing the EC [K] has a greater effect on E ank thus the RMP because of the ratio. Changing EC 5 to 6 is a 20% change, while changing the IC 150 to 149 is a 0.7% change. This can be confirmed by the Nernst Equation. Role of NaK Pumps RMP is almost E ,Kwhich shows that K has the greatest influence on membrane potential, but because the RMP is less than E K it is suggested that there must be a leakage of K. o Leakage channels are always open. Electrogenic Effect: the continuous maintenance of ion concentration through unequal transport of (+) ions because 3Na for every 2K, leakage is countered and it makes the inside “less” positive or negatively charged. o This is minimal on RMP. o Ion leakage and the electrogenic effect result in the RMP of about 70 mV. Cell Signaling – communication between cells (intercellular) by the release of regulatory molecules into extracellular environment. Categories: o Paracrine: within the organ and releases regulatory molecules for local mechanisms on nearby cells o Synaptic: functional connection between synapse and target organ through which neurotransmitters are released by axon endings. o Endocrine: long distance communication through hormones released into blood or lymph circulation o Autocrine: product feeds back into itself Gap Junctions allow adjoining cells to direct communication by diffusion and can be regulated. Regulatory Molecules Released by signaling cells or organs, then, will bind to the target cell for the response, but the target cell must display the specific receptor protein for that signaling/regulatory molecule. Location of the receptors are affected by the nature of the signaling molecule. o If the molecule is small and nonpolar (lipiidsoluble) it can pass freely through the PM so its receptor will be located intracellulary either in the cytoplasm or the nucleus o If the molecule is polar (watersoluble), then the receptor is imbedded in the PM because it cannot pass through the PM. Signal Transduction Pathways The mechanism for watersoluble messengers is the second messenger system. o When the regulatory molecule cannot enter the cell, the second messenger is sent into the cytoplasm from the receptor proteins in the PM. Gproteins shuttle between receptors and membrane effector proteins to activate the effector proteins and are made up of three subunits: , , and . o It takes energy and splits into () and (), through which either subunits can temporarily activate the enzyme or operate the ion channel. The mechanism for a lipidsoluble messenger is that the messenger will go through the PM and enter the nucleus. It binds to a receptor (transcription factor) that generates a message to cause a cellular response. Cessation of Activity in Signal Transduction Cessation is important because chronic overstimulation can be detrimental to the cell so it is necessary for the cell to respond if a stop signal is present. Key event is stopping receptor (R) activation: o decrease conc. of regulatory molecule o R becomes chemically alter, which lowers the affinity for regulatory molecule, which means the molecule does not bind as much. o R becomes phosphorylated, which prevents G protein binding o Rlingand complex endocytosed to remove R from PM Overall, there are ways to stop and/or depress signal transduction.
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